Variant 11-12517692-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018222.5(PARVA):c.950C>T(p.Pro317Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000487 in 1,600,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

PARVA
NM_018222.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.913

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARVA	NM_018222.5 linkuse as main transcript	c.950C>T	p.Pro317Leu	missense_variant	11/13	ENST00000334956.15
PARVA	XM_005253015.4 linkuse as main transcript	c.818C>T	p.Pro273Leu	missense_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARVA	ENST00000334956.15 linkuse as main transcript	c.950C>T	p.Pro317Leu	missense_variant	11/13	1	NM_018222.5	P1	Q9NVD7-1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.0000924

AC:

AN:

227382

Hom.:

AF XY:

0.0000734

AC XY:

AN XY:

122692

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000277

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000591

Gnomad SAS exome

AF:

0.000147

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000590

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.0000476

AC:

AN:

1448678

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

719098

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000255

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000353

Gnomad4 OTH exome

AF:

0.0000834

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000441

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.0000844

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000744

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

Dec 04, 2023

The c.1070C>T (p.P357L) alteration is located in exon 11 (coding exon 11) of the PARVA gene. This alteration results from a C to T substitution at nucleotide position 1070, causing the proline (P) at amino acid position 357 to be replaced by a leucine (L). 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

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Uncertain

0.10

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Pathogenic

0.92

D;.

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;.

M_CAP

Uncertain

0.097

MetaRNN

Pathogenic

0.91

D;D

MetaSVM

Uncertain

0.19

MutationAssessor

Pathogenic

3.6

H;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.86

REVEL

Pathogenic

0.69

Polyphen

1.0

D;.

MutPred

0.83

Loss of phosphorylation at T316 (P = 0.1264);.;

MVP

0.80

MPC

1.1

ClinPred

0.94

GERP RS

4.8

Varity_R

0.89

gMVP

0.81

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