rs369159531

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7

The NM_014845.6(FIG4):c.918C>T(p.Cys306Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,612,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

FIG4
NM_014845.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.504

Publications

0 publications found

Variant links:

Genes affected

FIG4 (HGNC:16873): (FIG4 phosphoinositide 5-phosphatase) The protein encoded by this gene belongs to the SAC domain-containing protein gene family. The SAC domain, approximately 400 amino acids in length and consisting of seven conserved motifs, has been shown to possess phosphoinositide phosphatase activity. The yeast homolog, Sac1p, is involved in the regulation of various phosphoinositides, and affects diverse cellular functions such as actin cytoskeleton organization, Golgi function, and maintenance of vacuole morphology. Membrane-bound phosphoinositides function as signaling molecules and play a key role in vesicle trafficking in eukaryotic cells. Mutations in this gene have been associated with Charcot-Marie-Tooth disease, type 4J. [provided by RefSeq, Jul 2008]

FIG4 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Illumina
Charcot-Marie-Tooth disease type 4J
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Laboratory for Molecular Medicine
Yunis-Varon syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
amyotrophic lateral sclerosis type 11
Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
bilateral parasagittal parieto-occipital polymicrogyria
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FIG4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 6-109743151-C-T is Benign according to our data. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109743151-C-T is described in CliVar as Likely_benign. Clinvar id is 543511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.504 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIG4	NM_014845.6 link	c.918C>T	p.Cys306Cys	synonymous_variant	Exon 9 of 23	ENST00000230124.8	NP_055660.1	Q92562
FIG4	XM_011536281.4 link	c.855C>T	p.Cys285Cys	synonymous_variant	Exon 9 of 23		XP_011534583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIG4	ENST00000230124.8 link	c.918C>T	p.Cys306Cys	synonymous_variant	Exon 9 of 23	1	NM_014845.6	ENSP00000230124.4		Q92562

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000678

AC:

AN:

250784

AF XY:

0.0000590

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1460586

Hom.:

Cov.:

AF XY:

0.0000372

AC XY:

AN XY:

726644

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33400

American (AMR)

AF:

0.0000224

AC:

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.000278

AC:

AN:

39618

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000306

AC:

AN:

1111154

Other (OTH)

AF:

0.0000497

AC:

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000889

Hom.:

Bravo

AF:

0.0000529

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease

Benign:1

Molecular Genetics Laboratory, London Health Sciences Centre

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FIG4: BP4, BP7 -

Charcot-Marie-Tooth disease type 4

Benign:1

Dec 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.38

(source)

DANN

Benign

0.46

PhyloP100

-0.50

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over