22-43999571-T-G

Variant names:

• chr22-43999571-T-G
• rs1007863
• ENST00000406477.7:c.109T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000406477.7(PARVB):​c.109T>G​(p.Trp37Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,459,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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: 0.0000048 (0 hom.)
• Consequence: PARVB ENST00000406477.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• 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]

SAMM50 (HGNC:24276): (SAMM50 sorting and assembly machinery component) This gene encodes a component of the Sorting and Assembly Machinery (SAM) of the mitochondrial outer membrane. The Sam complex functions in the assembly of beta-barrel proteins into the outer mitochondrial membrane.[provided by RefSeq, Jun 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05703011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARVB	NM_001003828.3	c.109T>G	p.Trp37Gly	missense_variant	Exon 2 of 14		NP_001003828.1
PARVB	XM_024452236.2	c.109T>G	p.Trp37Gly	missense_variant	Exon 2 of 13		XP_024308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000406477.7	c.109T>G	p.Trp37Gly	missense_variant	Exon 2 of 14	1		ENSP00000384515.3
SAMM50	ENST00000465768.1	n.79+9165T>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1459898 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726358

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1110238

Other (OTH) AF: 0.00 AC: 0 AN: 60296

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.091
DANN	Benign	0.42
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
PhyloP100		-2.5
PROVEAN	Benign	0.14	N
REVEL	Benign	0.0030
Sift	Benign	0.23	T
Sift4G	Pathogenic	0.0	D
Vest4		0.15
ClinPred		0.079	T
GERP RS		-3.8
PromoterAI		-0.053	Neutral
gMVP		0.053
Mutation Taster		=96/4	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1007863; hg19: chr22-44395451;