Variant chr11-12504399-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018222.5(PARVA):c.627C>A(p.Asp209Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,460,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.000019 ( 0 hom. )

Consequence

PARVA
NM_018222.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.353

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:

PARVA (HGNC:):

PARVA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045698762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARVA	NM_018222.5 linkuse as main transcript	c.627C>A	p.Asp209Glu	missense_variant	6/13	ENST00000334956.15	NP_060692.3	Q9NVD7-1
PARVA	XM_005253015.4 linkuse as main transcript	c.495C>A	p.Asp165Glu	missense_variant	6/13		XP_005253072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PARVA	ENST00000334956.15 linkuse as main transcript	c.627C>A	p.Asp209Glu	missense_variant	6/13	1	NM_018222.5	ENSP00000334008.9	Q9NVD7-1
PARVA	ENST00000528916.1 linkuse as main transcript	c.519C>A	p.Asp173Glu	missense_variant	6/8	5		ENSP00000435860.1	E9PS97
PARVA	ENST00000533345.5 linkuse as main transcript	n.604C>A		non_coding_transcript_exon_variant	6/8	5
PARVA	ENST00000533392.1 linkuse as main transcript	n.*44C>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1460740

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726694

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000243

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

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

Jan 30, 2024

The c.747C>A (p.D249E) alteration is located in exon 6 (coding exon 6) of the PARVA gene. This alteration results from a C to A substitution at nucleotide position 747, causing the aspartic acid (D) at amino acid position 249 to be replaced by a glutamic acid (E). 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

0.15

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.091

T;.;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.57

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.86

D;.;D

M_CAP

Benign

0.0078

MetaRNN

Benign

0.046

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.3

N;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

1.4

.;.;N

REVEL

Benign

0.14

Sift

Benign

1.0

.;.;T

Sift4G

Benign

1.0

.;.;T

Polyphen

0.0

B;.;.

MutPred

0.26

Gain of MoRF binding (P = 0.2601);.;.;

MVP

0.11

MPC

0.32

ClinPred

0.30

GERP RS

3.1

Varity_R

0.095

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

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