PARVG p.Gly27Glu

Variant names:

• chr22-44183409-G-A
• rs779565498
• NM_022141.7:c.79+1G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-44183409-G-A
• chr22-44183409-GA-AG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022141.7(PARVG):​c.79+1G>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.000000692 in 1,446,024 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PARVG NM_022141.7 splice_donor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.74
• 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 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022141.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVG	NM_022141.7	MANE Select	c.79+1G>A		splice_donor intron	N/A	NP_071424.1	Q9HBI0-1
	PARVG	NM_001137605.3		c.79+1G>A		splice_donor intron	N/A	NP_001131077.1	Q9HBI0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVG	ENST00000444313.8	TSL:1 MANE Select	c.79+1G>A		splice_donor intron	N/A	ENSP00000391583.2	Q9HBI0-1
	PARVG	ENST00000453888.7	TSL:1	n.299+1G>A		splice_donor intron	N/A
	PARVG	ENST00000417767.1	TSL:2	c.80G>A	p.Gly27Asp	missense	Exon 2 of 2	ENSP00000407199.1	B0QYN0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1446024 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 718290

African (AFR) AF: 0.00 AC: 0 AN: 32962

American (AMR) AF: 0.00 AC: 0 AN: 41508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25456

East Asian (EAS) AF: 0.00 AC: 0 AN: 39144

South Asian (SAS) AF: 0.00 AC: 0 AN: 83164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106866

Other (OTH) AF: 0.0000167 AC: 1 AN: 59772

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	0.0099	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	34
DANN	Uncertain	0.98
Eigen	Pathogenic	0.74
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.76	D
PhyloP100		3.7
Mutation Taster		=30/70	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.88
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.73		Position offset: 15
DS_DL_spliceai		0.99		Position offset: -1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs779565498; hg19: chr22-44579289;