Variant 11-12527851-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018222.5(PARVA):c.1045A>G(p.Ile349Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 1,612,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

PARVA
NM_018222.5 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

Variant links:

Genes affected

PARVA (HGNC:14652): (parvin alpha) This gene encodes a member of the parvin family of actin-binding proteins. Parvins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. The encoded protein is part of the integrin-linked kinase signaling complex and plays a role in cell adhesion, motility and survival. [provided by RefSeq, Dec 2010]

PARVA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.25883532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARVA	NM_018222.5 linkuse as main transcript	c.1045A>G	p.Ile349Val	missense_variant, splice_region_variant	13/13	ENST00000334956.15
PARVA	XM_005253015.4 linkuse as main transcript	c.913A>G	p.Ile305Val	missense_variant, splice_region_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARVA	ENST00000334956.15 linkuse as main transcript	c.1045A>G	p.Ile349Val	missense_variant, splice_region_variant	13/13	1	NM_018222.5	P1	Q9NVD7-1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000145

AC:

AN:

247800

Hom.:

AF XY:

0.000171

AC XY:

AN XY:

134574

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000287

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000171

AC:

249

AN:

1460280

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

114

AN XY:

726546

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000203

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000158

AC:

AN:

152050

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000278

Hom.:

Bravo

AF:

0.000170

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000240

AC:

ExAC

AF:

0.000149

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.1165A>G (p.I389V) alteration is located in exon 13 (coding exon 13) of the PARVA gene. This alteration results from a A to G substitution at nucleotide position 1165, causing the isoleucine (I) at amino acid position 389 to be replaced by a valine (V). 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

0.097

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Uncertain

-0.050

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.044

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.86

D;.

M_CAP

Benign

0.066

MetaRNN

Benign

0.26

T;T

MetaSVM

Uncertain

0.32

MutationAssessor

Benign

0.95

L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.69

REVEL

Uncertain

0.39

Polyphen

0.017

B;.

MVP

0.77

MPC

0.30

ClinPred

0.071

GERP RS

4.9

Varity_R

0.18

gMVP

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over