Genetic Variant FAM120C:c.1336-6G>A (chrX-54135117-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_017848.6(FAM120C):c.1336-6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,176,970 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000033 ( 0 hom. 13 hem. )

Consequence

FAM120C
NM_017848.6 splice_region, intron

Scores

Splicing: ADA: 0.00008143

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

Publications

0 publications found

Variant links:

Genes affected

FAM120C (HGNC:16949): (family with sequence similarity 120 member C) This gene encodes a potential transmembrane protein and lies in a region where mutations and deletions have been associated with intellectual disability and autism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

FAM120C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

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

BS2

High Hemizygotes in GnomAdExome4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FAM120C	NM_017848.6 link	c.1336-6G>A	splice_region_variant, intron_variant	Intron 6 of 15	ENST00000375180.7	NP_060318.4	Q9NX05-1
FAM120C	NM_001300788.2 link	c.1336-6G>A	splice_region_variant, intron_variant	Intron 6 of 13		NP_001287717.1	F8W881
FAM120C	XM_006724589.5 link	c.1336-6G>A	splice_region_variant, intron_variant	Intron 6 of 14		XP_006724652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM120C	ENST00000375180.7 link	c.1336-6G>A		splice_region_variant, intron_variant	Intron 6 of 15	1	NM_017848.6	ENSP00000364324.2		Q9NX05-1
FAM120C	ENST00000328235.4 link	c.1336-6G>A		splice_region_variant, intron_variant	Intron 6 of 13	1		ENSP00000329896.4		F8W881

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

112043

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000382

AC:

AN:

157200

AF XY:

0.0000405

show subpopulations

Gnomad AFR exome

AF:

0.0000792

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000767

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000413

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1064927

Hom.:

Cov.:

AF XY:

0.0000382

AC XY:

AN XY:

340505

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

25269

American (AMR)

AF:

0.00

AC:

AN:

30528

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17646

East Asian (EAS)

AF:

0.000101

AC:

AN:

29787

South Asian (SAS)

AF:

0.0000620

AC:

AN:

48397

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39627

Middle Eastern (MID)

AF:

0.000549

AC:

AN:

3641

European-Non Finnish (NFE)

AF:

0.0000267

AC:

AN:

825499

Other (OTH)

AF:

0.0000449

AC:

AN:

44533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00000893

AC:

AN:

112043

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34207

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30870

American (AMR)

AF:

0.00

AC:

AN:

10514

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3579

South Asian (SAS)

AF:

0.00

AC:

AN:

2698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53232

Other (OTH)

AF:

0.00

AC:

AN:

1509

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Sep 01, 2018

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

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

(source)

DANN

Benign

0.67

PhyloP100

1.1

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000081

dbscSNV1_RF

Benign

0.0040

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

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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