6-109825100-G-A

Position:

chr6-109825100-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014845.6(FIG4):c.2559G>A(p.Ser853Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,611,466 control chromosomes in the GnomAD database, including 144,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11207 hom., cov: 32)

Exomes 𝑓: 0.42 ( 133281 hom. )

Consequence

FIG4
NM_014845.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: -2.65

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 links:

FIG4 (HGNC:):

FIG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 6-109825100-G-A is Benign according to our data. Variant chr6-109825100-G-A is described in ClinVar as [Benign]. Clinvar id is 260449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109825100-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.65 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIG4	NM_014845.6 linkuse as main transcript	c.2559G>A	p.Ser853Ser	synonymous_variant	23/23	ENST00000230124.8	NP_055660.1	Q92562
FIG4	XM_011536281.4 linkuse as main transcript	c.2496G>A	p.Ser832Ser	synonymous_variant	23/23		XP_011534583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FIG4	ENST00000230124.8 linkuse as main transcript	c.2559G>A	p.Ser853Ser	synonymous_variant	23/23	1	NM_014845.6	ENSP00000230124.4		Q92562

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54508

AN:

151896

Hom.:

11209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.476

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.590

Gnomad SAS

AF:

0.551

Gnomad FIN

AF:

0.411

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.412

Gnomad OTH

AF:

0.401

GnomAD3 exomes

AF:

0.439

AC:

110072

AN:

250872

Hom.:

25733

AF XY:

0.447

AC XY:

60563

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.495

Gnomad ASJ exome

AF:

0.483

Gnomad EAS exome

AF:

0.575

Gnomad SAS exome

AF:

0.549

Gnomad FIN exome

AF:

0.422

Gnomad NFE exome

AF:

0.411

Gnomad OTH exome

AF:

0.454

GnomAD4 exome

AF:

0.422

AC:

615174

AN:

1459452

Hom.:

133281

Cov.:

AF XY:

0.426

AC XY:

309595

AN XY:

726214

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.495

Gnomad4 ASJ exome

AF:

0.483

Gnomad4 EAS exome

AF:

0.566

Gnomad4 SAS exome

AF:

0.548

Gnomad4 FIN exome

AF:

0.420

Gnomad4 NFE exome

AF:

0.410

Gnomad4 OTH exome

AF:

0.437

GnomAD4 genome

AF:

0.359

AC:

54514

AN:

152014

Hom.:

11207

Cov.:

AF XY:

0.366

AC XY:

27153

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.476

Gnomad4 ASJ

AF:

0.489

Gnomad4 EAS

AF:

0.591

Gnomad4 SAS

AF:

0.550

Gnomad4 FIN

AF:

0.411

Gnomad4 NFE

AF:

0.412

Gnomad4 OTH

AF:

0.404

Alfa

AF:

0.410

Hom.:

12951

Bravo

AF:

0.352

Asia WGS

AF:

0.550

AC:

1909

AN:

3478

EpiCase

AF:

0.432

EpiControl

AF:

0.434

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Amyotrophic lateral sclerosis type 11

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

Charcot-Marie-Tooth disease type 4J

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

Yunis-Varon syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

Bilateral parasagittal parieto-occipital polymicrogyria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Charcot-Marie-Tooth disease type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.17

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over