rs2275047

Positions:

• chr10-97679784-G-A
• chr10-97679784-G-C

Variant summary

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

The NM_021732.3(AVPI1):​c.122C>T​(p.Ala41Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A41G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AVPI1 NM_021732.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

Genes affected

AVPI1 (HGNC:30898): (arginine vasopressin induced 1) Predicted to act upstream of or within positive regulation of MAPK cascade. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09175077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AVPI1	NM_021732.3	c.122C>T	p.Ala41Val	missense_variant	2/3	ENST00000370626.4
AVPI1	XM_017016494.2	c.122C>T	p.Ala41Val	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AVPI1	ENST00000370626.4	c.122C>T	p.Ala41Val	missense_variant	2/3	1	NM_021732.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.057
Sift	Benign	0.13	T
Sift4G	Benign	0.19	T
Polyphen		0.0040	B
Vest4		0.10
MutPred		0.25		Loss of disorder (P = 0.0676);
MVP		0.38
MPC		0.028
ClinPred		0.32	T
GERP RS		5.1
Varity_R		0.10
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs2275047; hg19: chr10-99439541;