10-97679784-G-C

Position:

• chr10-97679784-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021732.3(AVPI1):​c.122C>G​(p.Ala41Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,613,232 control chromosomes in the GnomAD database, including 148,052 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.47 (18234 hom., cov: 32)
  • Exomes 𝑓: 0.42 (129818 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6955511E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AVPI1	NM_021732.3	c.122C>G	p.Ala41Gly	missense_variant	2/3	ENST00000370626.4
AVPI1	XM_017016494.2	c.122C>G	p.Ala41Gly	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AVPI1	ENST00000370626.4	c.122C>G	p.Ala41Gly	missense_variant	2/3	1	NM_021732.3	P1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71980 AN: 151940 Hom.: 18187 Cov.: 32

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.436

GnomAD3 exomes AF: 0.430 AC: 107343 AN: 249424 Hom.: 23898 AF XY: 0.429 AC XY: 57885 AN XY: 135076

Gnomad AFR exome AF: 0.656

Gnomad AMR exome AF: 0.441

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.505

Gnomad SAS exome AF: 0.508

Gnomad FIN exome AF: 0.362

Gnomad NFE exome AF: 0.385

Gnomad OTH exome AF: 0.394

GnomAD4 exome AF: 0.418 AC: 610495 AN: 1461174 Hom.: 129818 Cov.: 73 AF XY: 0.420 AC XY: 304937 AN XY: 726884

Gnomad4 AFR exome AF: 0.669

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.501

Gnomad4 SAS exome AF: 0.509

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.404

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.474 AC: 72092 AN: 152058 Hom.: 18234 Cov.: 32 AF XY: 0.472 AC XY: 35056 AN XY: 74348

Gnomad4 AFR AF: 0.660

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.437

Alfa AF: 0.409 Hom.: 9768

Bravo AF: 0.486

TwinsUK AF: 0.402 AC: 1492

ALSPAC AF: 0.403 AC: 1555

ESP6500AA AF: 0.646 AC: 2846

ESP6500EA AF: 0.396 AC: 3408

ExAC AF: 0.436 AC: 52939

Asia WGS AF: 0.510 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	18
DANN	Benign	0.79
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.000017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.87	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.044
MPC		0.023
ClinPred		0.0050	T
GERP RS		5.1
Varity_R		0.067
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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; COSMIC: COSV65697960; COSMIC: COSV65697960;