NM_000820.4:c.1640A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000820.4(GAS6):​c.1640A>C​(p.Lys547Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

GAS6
NM_000820.4 missense

Scores

11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99
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-AS1 (HGNC:39826): (GAS6 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GAS6NM_000820.4 linkc.1640A>C p.Lys547Thr missense_variant Exon 13 of 15 ENST00000327773.7 NP_000811.1 Q14393-2
GAS6-AS1NR_044995.2 linkn.82+7697T>G intron_variant Intron 1 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GAS6ENST00000327773.7 linkc.1640A>C p.Lys547Thr missense_variant Exon 13 of 15 1 NM_000820.4 ENSP00000331831.6 Q14393-2
GAS6ENST00000480426.5 linkn.1795A>C non_coding_transcript_exon_variant Exon 5 of 7 2
GAS6ENST00000610073.1 linkn.1460A>C non_coding_transcript_exon_variant Exon 7 of 9 2
GAS6-AS1ENST00000458001.2 linkn.62+7697T>G intron_variant Intron 1 of 4 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 12, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1640A>C (p.K547T) alteration is located in exon 13 (coding exon 13) of the GAS6 gene. This alteration results from a A to C substitution at nucleotide position 1640, causing the lysine (K) at amino acid position 547 to be replaced by a threonine (T). 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
Uncertain
0.49
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Uncertain
23
DANN
Uncertain
1.0
Eigen
Benign
-0.0099
Eigen_PC
Benign
-0.044
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.90
D
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.73
D
MetaSVM
Benign
-0.44
T
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-2.5
D
REVEL
Uncertain
0.60
Sift
Benign
0.077
T
Sift4G
Benign
0.13
T
Vest4
0.69
MVP
0.75
MPC
0.95
ClinPred
0.84
D
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.18
gMVP
0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-114526361; API