Genetic Variant NM_000820.4:c.1780A>T (chr13-113822060-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000820.4(GAS6):c.1780A>T(p.Arg594Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GAS6
NM_000820.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.519

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24424839).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000820.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS6	NM_000820.4	MANE Select	c.1780A>T	p.Arg594Trp	missense	Exon 14 of 15	NP_000811.1	Q14393-2
	GAS6-AS1	NR_044995.2		n.82+6369T>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GAS6	ENST00000327773.7	TSL:1 MANE Select	c.1780A>T	p.Arg594Trp	missense	Exon 14 of 15	ENSP00000331831.6	Q14393-2
GAS6	ENST00000881729.1		c.2119A>T	p.Arg707Trp	missense	Exon 14 of 15	ENSP00000551788.1
GAS6	ENST00000881736.1		c.1972A>T	p.Arg658Trp	missense	Exon 14 of 15	ENSP00000551795.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1435870

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711818

African (AFR)

AF:

0.00

AC:

AN:

33256

American (AMR)

AF:

0.00

AC:

AN:

40212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25542

East Asian (EAS)

AF:

0.00

AC:

AN:

38720

South Asian (SAS)

AF:

0.00

AC:

AN:

82136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5320

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101260

Other (OTH)

AF:

0.00

AC:

AN:

59456

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.14

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.080

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.65

PhyloP100

0.52

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.3

REVEL

Benign

0.23

Sift

Uncertain

0.018

Sift4G

Uncertain

0.019

Vest4

0.33

MVP

0.50

MPC

0.63

ClinPred

0.63

GERP RS

2.1

Varity_R

0.17

gMVP

0.69

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over