rs3842776

Positions:

• chr22-44185808-G-C

Variant summary

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

The NM_022141.7(PARVG):​c.80G>C​(p.Gly27Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,460,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PARVG NM_022141.7 missense, splice_region
• Scores: Splicing: ADA: 0.9994
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.50

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARVG	NM_022141.7	c.80G>C	p.Gly27Ala	missense_variant, splice_region_variant	4/14	ENST00000444313.8	NP_071424.1
PARVG	NM_001137605.3	c.80G>C	p.Gly27Ala	missense_variant, splice_region_variant	4/14		NP_001131077.1
PARVG	XM_047441455.1	c.281G>C	p.Gly94Ala	missense_variant, splice_region_variant	3/11		XP_047297411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARVG	ENST00000444313.8	c.80G>C	p.Gly27Ala	missense_variant, splice_region_variant	4/14	1	NM_022141.7	ENSP00000391583.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000798 AC: 2 AN: 250686 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135578

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460934 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726818

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	35
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D;D;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.68	T;.;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.014	D;D;D
Sift4G	Benign	0.092	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.36
MutPred		0.23		Loss of stability (P = 0.0618);Loss of stability (P = 0.0618);Loss of stability (P = 0.0618);
MVP		0.72
MPC		0.61
ClinPred		0.74	D
GERP RS		4.8
Varity_R		0.27
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.97
SpliceAI score (max)		0.84		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.84		Position offset: 3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3842776; hg19: chr22-44581688;