chr22-44192079-T-G

Position:

• chr22-44192079-T-G

Variant summary

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

The NM_022141.7(PARVG):​c.535T>G​(p.Leu179Val) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PARVG NM_022141.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.736

Genes affected

PARVG (HGNC:14654): (parvin gamma) Members of the parvin family, including PARVG, are actin-binding proteins associated with focal contacts.[supplied by OMIM, Aug 2004]

PARVG (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=0.021673381).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARVG	NM_022141.7	c.535T>G	p.Leu179Val	missense_variant	8/14	ENST00000444313.8	NP_071424.1
PARVG	NM_001137605.3	c.535T>G	p.Leu179Val	missense_variant	8/14		NP_001131077.1
PARVG	XM_047441455.1	c.736T>G	p.Leu246Val	missense_variant	7/11		XP_047297411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARVG	ENST00000444313.8	c.535T>G	p.Leu179Val	missense_variant	8/14	1	NM_022141.7	ENSP00000391583.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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

Mar 27, 2023

The c.535T>G (p.L179V) alteration is located in exon 8 (coding exon 6) of the PARVG gene. This alteration results from a T to G substitution at nucleotide position 535, causing the leucine (L) at amino acid position 179 to be replaced by a valine (V). 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	0.056
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.73
DANN	Benign	0.072
DEOGEN2	Benign	0.038	T;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.22	T;.;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.022	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	-0.39	N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.1	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.97	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.062
MutPred		0.25		Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);
MVP		0.34
MPC		0.15
ClinPred		0.032	T
GERP RS		-1.5
Varity_R		0.023
gMVP		0.13

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.

Other links and lift over

hg19: chr22-44587959;