chr22-44119048-A-G

Variant names:

• chr22-44119048-A-G
• rs1418082663
• NM_013327.5:c.284A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013327.5(PARVB):​c.284A>G​(p.Asp95Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PARVB NM_013327.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.11
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARVB	NM_013327.5	c.284A>G	p.Asp95Gly	missense_variant	Exon 4 of 13	ENST00000338758.12	NP_037459.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000338758.12	c.284A>G	p.Asp95Gly	missense_variant	Exon 4 of 13	1	NM_013327.5	ENSP00000342492.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.383A>G (p.D128G) alteration is located in exon 5 (coding exon 5) of the PARVB gene. This alteration results from a A to G substitution at nucleotide position 383, causing the aspartic acid (D) at amino acid position 128 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	Benign	0.33
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	.;D;T;.;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.066
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Uncertain	0.089	D
MetaRNN	Uncertain	0.74	D;D;D;D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.9	.;M;.;.;.
PhyloP100		7.1
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.4	D;D;.;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0070	D;D;.;D;D
Sift4G	Uncertain	0.013	D;D;D;D;.
Polyphen		0.72	P;P;.;.;.
Vest4		0.75
MutPred		0.49		.;Loss of stability (P = 0.0755);.;.;.;
MVP		0.70
MPC		0.31
ClinPred		0.99	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.46
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs1418082663; hg19: chr22-44514928;