chr22-44193805-G-T

Position:

• chr22-44193805-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022141.7(PARVG):​c.565G>T​(p.Asp189Tyr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PARVG NM_022141.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.862

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11274621).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARVG	NM_022141.7	c.565G>T	p.Asp189Tyr	missense_variant	9/14	ENST00000444313.8	NP_071424.1
PARVG	NM_001137605.3	c.565G>T	p.Asp189Tyr	missense_variant	9/14		NP_001131077.1
PARVG	XM_047441455.1	c.766G>T	p.Asp256Tyr	missense_variant	8/11		XP_047297411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARVG	ENST00000444313.8	c.565G>T	p.Asp189Tyr	missense_variant	9/14	1	NM_022141.7	ENSP00000391583.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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 21, 2023

The c.565G>T (p.D189Y) alteration is located in exon 9 (coding exon 7) of the PARVG gene. This alteration results from a G to T substitution at nucleotide position 565, causing the aspartic acid (D) at amino acid position 189 to be replaced by a tyrosine (Y). 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	0.11
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Benign	0.11
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.56	T;.
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.69	N;N
REVEL	Benign	0.18
Sift	Benign	0.57	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.37	B;B
Vest4		0.19
MutPred		0.30		Gain of phosphorylation at D189 (P = 0.0132);Gain of phosphorylation at D189 (P = 0.0132);
MVP		0.68
MPC		0.19
ClinPred		1.0	D
GERP RS		0.90
Varity_R		0.047
gMVP		0.32

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: chr22-44589685;