12-63147477-C-T

Position:

• chr12-63147477-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000706.5(AVPR1A):​c.1139G>A​(p.Ser380Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AVPR1A NM_000706.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.35

Genes affected

AVPR1A (HGNC:895): (arginine vasopressin receptor 1A) The protein encoded by this gene acts as receptor for arginine vasopressin. This receptor belongs to the subfamily of G-protein coupled receptors which includes AVPR1B, V2R and OXT receptors. Its activity is mediated by G proteins which stimulate a phosphatidylinositol-calcium second messenger system. The receptor mediates cell contraction and proliferation, platelet aggregation, release of coagulation factor and glycogenolysis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2790493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AVPR1A	NM_000706.5	c.1139G>A	p.Ser380Asn	missense_variant	2/2	ENST00000299178.4	NP_000697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AVPR1A	ENST00000299178.4	c.1139G>A	p.Ser380Asn	missense_variant	2/2	1	NM_000706.5	ENSP00000299178.3
AVPR1A	ENST00000550940.1	c.482G>A	p.Ser161Asn	missense_variant	2/3	3		ENSP00000449822.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2024

The c.1139G>A (p.S380N) alteration is located in exon 2 (coding exon 2) of the AVPR1A gene. This alteration results from a G to A substitution at nucleotide position 1139, causing the serine (S) at amino acid position 380 to be replaced by an asparagine (N). 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	Benign	0.16
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.16
Sift	Uncertain	0.019	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.054	B;.
Vest4		0.35
MutPred		0.44		Loss of phosphorylation at S380 (P = 0.0248);.;
MVP		0.87
MPC		0.69
ClinPred		0.99	D
GERP RS		6.1
Varity_R		0.24
gMVP		0.59

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: chr12-63541257;