Variant chr13-113823403-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000820.4(GAS6):c.1625A>G(p.Tyr542Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GAS6
NM_000820.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.05

Variant links:

Genes affected

GAS6 (HGNC:4168): (growth arrest specific 6) This gene encodes a gamma-carboxyglutamic acid (Gla)-containing protein thought to be involved in the stimulation of cell proliferation. This gene is frequently overexpressed in many cancers and has been implicated as an adverse prognostic marker. Elevated protein levels are additionally associated with a variety of disease states, including venous thromboembolic disease, systemic lupus erythematosus, chronic renal failure, and preeclampsia. [provided by RefSeq, Aug 2014]

GAS6 links:

GAS6-AS1 (HGNC:39826): (GAS6 antisense RNA 1)

GAS6-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.903

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAS6	NM_000820.4 linkuse as main transcript	c.1625A>G	p.Tyr542Cys	missense_variant	13/15	ENST00000327773.7
GAS6-AS1	NR_044995.2 linkuse as main transcript	n.82+7712T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAS6	ENST00000327773.7 linkuse as main transcript	c.1625A>G	p.Tyr542Cys	missense_variant	13/15	1	NM_000820.4	P1	Q14393-2
GAS6-AS1	ENST00000458001.2 linkuse as main transcript	n.62+7712T>C		intron_variant, non_coding_transcript_variant		5
GAS6	ENST00000480426.5 linkuse as main transcript	n.1780A>G		non_coding_transcript_exon_variant	5/7	2
GAS6	ENST00000610073.1 linkuse as main transcript	n.1445A>G		non_coding_transcript_exon_variant	7/9	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459708

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726086

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

The c.1625A>G (p.Y542C) alteration is located in exon 13 (coding exon 13) of the GAS6 gene. This alteration results from a A to G substitution at nucleotide position 1625, causing the tyrosine (Y) at amino acid position 542 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.24

MetaRNN

Pathogenic

0.90

MetaSVM

Uncertain

0.072

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-4.3

REVEL

Pathogenic

0.71

Sift

Uncertain

0.029

Sift4G

Uncertain

0.019

Vest4

0.84

MVP

0.78

MPC

0.97

ClinPred

0.94

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.40

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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