22-44132960-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_013327.5(PARVB):​c.584C>G​(p.Ala195Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A195V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PARVB
NM_013327.5 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.92
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PARVBNM_013327.5 linkc.584C>G p.Ala195Gly missense_variant Exon 6 of 13 ENST00000338758.12 NP_037459.2 Q9HBI1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PARVBENST00000338758.12 linkc.584C>G p.Ala195Gly missense_variant Exon 6 of 13 1 NM_013327.5 ENSP00000342492.6 Q9HBI1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.683C>G (p.A228G) alteration is located in exon 7 (coding exon 7) of the PARVB gene. This alteration results from a C to G substitution at nucleotide position 683, causing the alanine (A) at amino acid position 228 to be replaced by a glycine (G). 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
Uncertain
0.41
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.77
.;D;T;.;.
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Pathogenic
0.82
D;D;D;D;D
MetaSVM
Benign
-0.35
T
MutationAssessor
Uncertain
2.9
.;M;.;.;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.4
D;D;.;D;D
REVEL
Benign
0.28
Sift
Benign
0.071
T;T;.;D;D
Sift4G
Benign
0.17
T;T;T;D;.
Polyphen
0.97
D;P;.;.;.
Vest4
0.74
MutPred
0.77
.;Loss of stability (P = 0.0256);.;.;.;
MVP
0.67
MPC
0.59
ClinPred
0.99
D
GERP RS
5.4
Varity_R
0.56
gMVP
0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-44528840; API