Genetic Variant PARVB:p.Thr204Met (chr22-44132987-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_013327.5(PARVB):c.611C>T(p.Thr204Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000062 ( 0 hom. )

Consequence

PARVB
NM_013327.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.87

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34607068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARVB	NM_013327.5 link	c.611C>T	p.Thr204Met	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
PARVB	ENST00000338758.12 link	c.611C>T	p.Thr204Met	missense_variant	Exon 6 of 13	1	NM_013327.5	ENSP00000342492.6		Q9HBI1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461534

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.710C>T (p.T237M) alteration is located in exon 7 (coding exon 7) of the PARVB gene. This alteration results from a C to T substitution at nucleotide position 710, causing the threonine (T) at amino acid position 237 to be replaced by a methionine (M). 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

0.072

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.16

.;T;T;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.35

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.90

.;L;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.4

N;N;.;N

REVEL

Benign

0.13

Sift

Benign

0.16

T;T;.;T

Sift4G

Benign

0.17

T;T;T;.

Polyphen

0.99

D;P;.;.

Vest4

0.43

MutPred

0.28

.;Gain of MoRF binding (P = 0.0785);.;.;

MVP

0.63

MPC

0.50

ClinPred

0.89

GERP RS

5.4

Varity_R

0.092

gMVP

0.30

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over