rs3842776

Variant names:

• chr22-44185808-G-A
• rs3842776
• NM_022141.7:c.80G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-44185808-G-A
• chr22-44185808-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_022141.7(PARVG):​c.80G>A​(p.Gly27Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000684 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: 6.8e-7 (0 hom.)
• Consequence: PARVG NM_022141.7 missense, splice_region
• Scores: Splicing: ADA: 0.9935
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.50
• Publications: 0 publications found

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]

ENSG00000279933 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARVG	NM_022141.7	c.80G>A	p.Gly27Glu	missense_variant, splice_region_variant	Exon 4 of 14	ENST00000444313.8	NP_071424.1
PARVG	NM_001137605.3	c.80G>A	p.Gly27Glu	missense_variant, splice_region_variant	Exon 4 of 14		NP_001131077.1
PARVG	XM_047441455.1	c.281G>A	p.Gly94Glu	missense_variant, splice_region_variant	Exon 3 of 11		XP_047297411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARVG	ENST00000444313.8	c.80G>A	p.Gly27Glu	missense_variant, splice_region_variant	Exon 4 of 14	1	NM_022141.7	ENSP00000391583.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460934 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726818

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111396

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.70	T;.;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.6	M;M;M
PhyloP100		5.5
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.015	D;D;D
Sift4G	Uncertain	0.026	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.37
MutPred		0.22		Gain of ubiquitination at K29 (P = 0.0352);Gain of ubiquitination at K29 (P = 0.0352);Gain of ubiquitination at K29 (P = 0.0352);
MVP		0.72
MPC		0.67
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.20
gMVP		0.46
Mutation Taster		=39/61	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.86
SpliceAI score (max)		0.58		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.58		Position offset: 3

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

Other links and lift over

dbSNP: rs3842776; hg19: chr22-44581688;