dbSNP rs1007863: PARVB:p.Trp37Arg (chr22-43999571-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000406477.7(PARVB):c.109T>A(p.Trp37Arg) 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. 13/18 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: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PARVB
ENST00000406477.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.50

Publications

38 publications found

Variant links:

Genes affected

PARVB (HGNC:14653): (parvin beta) This gene encodes a member of the parvin family of actin-binding proteins, which play a role in cytoskeleton organization and cell adhesion. These proteins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. This family member binds to alphaPIX and alpha-actinin, and it can inhibit the activity of integrin-linked kinase. This protein also functions in tumor suppression. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

PARVB links:

SAMM50 (HGNC:24276): (SAMM50 sorting and assembly machinery component) This gene encodes a component of the Sorting and Assembly Machinery (SAM) of the mitochondrial outer membrane. The Sam complex functions in the assembly of beta-barrel proteins into the outer mitochondrial membrane.[provided by RefSeq, Jun 2011]

SAMM50 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034793705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARVB	NM_001003828.3 link	c.109T>A	p.Trp37Arg	missense_variant	Exon 2 of 14		NP_001003828.1	Q9HBI1-2
PARVB	XM_024452236.2 link	c.109T>A	p.Trp37Arg	missense_variant	Exon 2 of 13		XP_024308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000406477.7 link	c.109T>A	p.Trp37Arg	missense_variant	Exon 2 of 14	1		ENSP00000384515.3		Q9HBI1-2
SAMM50	ENST00000465768.1 link	n.79+9165T>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1459898

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726358

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110238

Other (OTH)

AF:

0.00

AC:

AN:

60296

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

37051

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.042

(source)

DANN

Benign

0.44

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0064

LIST_S2

Benign

0.16

M_CAP

Benign

0.0012

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.96

PhyloP100

-2.5

PROVEAN

Benign

0.68

REVEL

Benign

0.0050

Sift

Benign

0.97

Sift4G

Pathogenic

0.0

Polyphen

0.0070

Vest4

0.012

MutPred

0.38

Gain of methylation at W37 (P = 0.0153);

MVP

0.11

MPC

0.29

ClinPred

0.054

GERP RS

-3.8

PromoterAI

-0.035

Neutral

(source)

gMVP

0.052

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over