13-113827141-G-C

Variant names:

• chr13-113827141-G-C
• rs1803628
• NM_000820.4:c.1332C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_000820.4(GAS6):​c.1332C>G​(p.Cys444Trp) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GAS6 NM_000820.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

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

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAS6	NM_000820.4	c.1332C>G	p.Cys444Trp	missense_variant	Exon 12 of 15	ENST00000327773.7	NP_000811.1
GAS6-AS1	NR_044995.2	n.83-6351G>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS6	ENST00000327773.7	c.1332C>G	p.Cys444Trp	missense_variant	Exon 12 of 15	1	NM_000820.4	ENSP00000331831.6
GAS6	ENST00000480426.5	n.1487C>G		non_coding_transcript_exon_variant	Exon 4 of 7	2
GAS6	ENST00000610073.1	n.1152C>G		non_coding_transcript_exon_variant	Exon 6 of 9	2
GAS6-AS1	ENST00000458001.2	n.63-6351G>C		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Benign	21
DANN	Benign	0.94
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.67
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.46	D
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-9.9	D
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.94
MVP		0.68
MPC		1.0
ClinPred		0.97	D
GERP RS		-1.3
Varity_R		0.93
gMVP		0.93

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

Other links and lift over

dbSNP: rs1803628; hg19: chr13-114530114;