12-63150720-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000706.5(AVPR1A):c.117C>G(p.Asn39Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,452,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: AVPR1A NM_000706.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.180

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07122594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AVPR1A	NM_000706.5	c.117C>G	p.Asn39Lys	missense_variant	1/2	ENST00000299178.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AVPR1A	ENST00000299178.4	c.117C>G	p.Asn39Lys	missense_variant	1/2	1	NM_000706.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1452110 Hom.: 0 Cov.: 34 AF XY: 0.00000415 AC XY: 3 AN XY: 722830

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Sep 06, 2022

The c.117C>G (p.N39K) alteration is located in exon 1 (coding exon 1) of the AVPR1A gene. This alteration results from a C to G substitution at nucleotide position 117, causing the asparagine (N) at amino acid position 39 to be replaced by a lysine (K). 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	0.083
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	6.7
Dann	Benign	0.71
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.042
Sift	Benign	0.13	T
Sift4G	Benign	0.92	T
Polyphen		0.0050	B
Vest4		0.061
MutPred		0.39		Gain of catalytic residue at P41 (P = 0.0016);
MVP		0.29
MPC		0.91
ClinPred		0.086	T
GERP RS		-2.1
Varity_R		0.071
gMVP		0.25

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: chr12-63544500;