chr22-44093988-T-C

Variant names:

• chr22-44093988-T-C
• rs1983609
• NM_013327.5:c.173T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003828.3(PARVB):​c.272T>C​(p.Val91Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 1,610,808 control chromosomes in the GnomAD database, including 492,790 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.83 (52574 hom., cov: 34)
  • Exomes 𝑓: 0.77 (440216 hom.)
• Consequence: PARVB NM_001003828.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• Publications: 38 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.987892E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003828.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	NM_013327.5	MANE Select	c.173T>C	p.Val58Ala	missense	Exon 2 of 13	NP_037459.2
	PARVB	NM_001003828.3		c.272T>C	p.Val91Ala	missense	Exon 3 of 14	NP_001003828.1
	PARVB	NM_001243385.2		c.62T>C	p.Val21Ala	missense	Exon 2 of 13	NP_001230314.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	ENST00000338758.12	TSL:1 MANE Select	c.173T>C	p.Val58Ala	missense	Exon 2 of 13	ENSP00000342492.6
	PARVB	ENST00000406477.7	TSL:1	c.272T>C	p.Val91Ala	missense	Exon 3 of 14	ENSP00000384515.3
	PARVB	ENST00000404989.1	TSL:1	c.62T>C	p.Val21Ala	missense	Exon 2 of 13	ENSP00000384353.1

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125534 AN: 152150 Hom.: 52512 Cov.: 34

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.804

GnomAD2 exomes AF: 0.809 AC: 203028 AN: 250930 AF XY: 0.801

Gnomad AFR exome AF: 0.954

Gnomad AMR exome AF: 0.886

Gnomad ASJ exome AF: 0.817

Gnomad EAS exome AF: 0.965

Gnomad FIN exome AF: 0.728

Gnomad NFE exome AF: 0.760

Gnomad OTH exome AF: 0.780

GnomAD4 exome AF: 0.775 AC: 1129932 AN: 1458540 Hom.: 440216 Cov.: 35 AF XY: 0.774 AC XY: 561764 AN XY: 725740

African (AFR) AF: 0.960 AC: 32079 AN: 33432

American (AMR) AF: 0.879 AC: 39236 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 21139 AN: 26098

East Asian (EAS) AF: 0.965 AC: 38288 AN: 39676

South Asian (SAS) AF: 0.794 AC: 68411 AN: 86138

European-Finnish (FIN) AF: 0.729 AC: 38908 AN: 53352

Middle Eastern (MID) AF: 0.771 AC: 4442 AN: 5762

European-Non Finnish (NFE) AF: 0.757 AC: 839531 AN: 1109194

Other (OTH) AF: 0.795 AC: 47898 AN: 60256

GnomAD4 genome AF: 0.825 AC: 125654 AN: 152268 Hom.: 52574 Cov.: 34 AF XY: 0.825 AC XY: 61423 AN XY: 74446

African (AFR) AF: 0.953 AC: 39611 AN: 41576

American (AMR) AF: 0.834 AC: 12759 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2824 AN: 3470

East Asian (EAS) AF: 0.964 AC: 4983 AN: 5170

South Asian (SAS) AF: 0.801 AC: 3868 AN: 4826

European-Finnish (FIN) AF: 0.740 AC: 7855 AN: 10608

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51175 AN: 67998

Other (OTH) AF: 0.803 AC: 1698 AN: 2114

Alfa AF: 0.778 Hom.: 209980

Bravo AF: 0.841

TwinsUK AF: 0.767 AC: 2843

ALSPAC AF: 0.766 AC: 2952

ESP6500AA AF: 0.948 AC: 4179

ESP6500EA AF: 0.760 AC: 6540

ExAC AF: 0.810 AC: 98301

Asia WGS AF: 0.874 AC: 3035 AN: 3478

EpiCase AF: 0.757

EpiControl AF: 0.759

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.6
DANN	Benign	0.43
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	8.0e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		0.27
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.34	N
REVEL	Benign	0.041
Sift	Benign	0.80	T
Sift4G	Benign	0.67	T
Polyphen		0.0030	B
Vest4		0.035
MPC		0.20
ClinPred		0.00043	T
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.018
gMVP		0.095
Mutation Taster		=99/1	polymorphism (auto)

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: rs1983609; hg19: chr22-44489868; COSMIC: COSV58690840;