22-43999619-C-T

Position:

• chr22-43999619-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001003828.3(PARVB):​c.157C>T​(p.Leu53Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: PARVB NM_001003828.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.67

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:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04876265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARVB	NM_001003828.3	c.157C>T	p.Leu53Phe	missense_variant	2/14		NP_001003828.1
PARVB	XM_024452236.2	c.157C>T	p.Leu53Phe	missense_variant	2/13		XP_024308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000406477.7	c.157C>T	p.Leu53Phe	missense_variant	2/14	1		ENSP00000384515.3
SAMM50	ENST00000465768.1	n.79+9213C>T		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.157C>T (p.L53F) alteration is located in exon 2 (coding exon 2) of the PARVB gene. This alteration results from a C to T substitution at nucleotide position 157, causing the leucine (L) at amino acid position 53 to be replaced by a phenylalanine (F). 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
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.37
DANN	Benign	0.97
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.99	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.030
Sift	Benign	0.053	T
Sift4G	Benign	0.14	T
Polyphen		0.054	B
Vest4		0.061
MutPred		0.10		Loss of phosphorylation at S51 (P = 0.1658);
MVP		0.088
MPC		0.19
ClinPred		0.051	T
GERP RS		-3.3
gMVP		0.032

Splicing

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: chr22-44395499;