12-63147571-T-A

Variant names:

• chr12-63147571-T-A
• rs376412201
• NM_000706.5:c.1045A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000706.5(AVPR1A):​c.1045A>T​(p.Met349Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M349K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AVPR1A NM_000706.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17
• Publications: 0 publications found

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]

AVPR1A Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000706.5. 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
	AVPR1A	NM_000706.5	MANE Select	c.1045A>T	p.Met349Leu	missense	Exon 2 of 2	NP_000697.1	P37288

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVPR1A	ENST00000299178.4	TSL:1 MANE Select	c.1045A>T	p.Met349Leu	missense	Exon 2 of 2	ENSP00000299178.3	P37288
	AVPR1A	ENST00000550940.1	TSL:3	c.388A>T	p.Met130Leu	missense	Exon 2 of 3	ENSP00000449822.1	F8VW98

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.2
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.18
Sift	Benign	0.11	T
Sift4G	Benign	0.14	T
Polyphen		0.30	B
Vest4		0.47
MutPred		0.61		Gain of catalytic residue at W346 (P = 0)
MVP		0.60
MPC		0.66
ClinPred		0.90	D
GERP RS		5.8
Varity_R		0.41
gMVP		0.73
Mutation Taster		=35/65	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.38		Position offset: -11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs376412201; hg19: chr12-63541351;