chr17-65014362-G-C

Position:

• chr17-65014362-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_006572.6(GNA13):​c.1029C>G​(p.Tyr343Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNA13 NM_006572.6 stop_gained
• Clinical Significance: - - O:1
• Conservation: PhyloP100: 4.94

Genes affected

GNA13 (HGNC:4381): (G protein subunit alpha 13) Predicted to enable D5 dopamine receptor binding activity; G-protein beta/gamma-subunit complex binding activity; and GTPase activity. Predicted to be involved in several processes, including Rho protein signal transduction; activation of phospholipase D activity; and multicellular organism aging. Predicted to act upstream of or within several processes, including branching involved in blood vessel morphogenesis; negative regulation of vascular associated smooth muscle cell migration; and negative regulation of vascular associated smooth muscle cell proliferation. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0926 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA13	NM_006572.6	c.1029C>G	p.Tyr343Ter	stop_gained	4/4	ENST00000439174.7
GNA13	NM_001282425.2	c.744C>G	p.Tyr248Ter	stop_gained	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA13	ENST00000439174.7	c.1029C>G	p.Tyr343Ter	stop_gained	4/4	1	NM_006572.6	P1
GNA13	ENST00000541118.1	c.744C>G	p.Tyr248Ter	stop_gained	4/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: -

Submissions summary: Other:1

Revision: -

Submissions by phenotype

Neoplasm Other:1

-, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Jul 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.94	D
MutationTaster	Benign	1.0	D;D
Vest4		0.77
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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: chr17-63010480;