rs372522213

Variant names:

• chr7-55492399-C-G
• rs372522213
• NM_030796.5:c.211G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-55492399-C-G
• chr7-55492399-C-T

Variant summary

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

The NM_030796.5(VOPP1):​c.211G>C​(p.Val71Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V71M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VOPP1 NM_030796.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.91
• Publications: 0 publications found

Genes affected

VOPP1 (HGNC:34518): (VOPP1 WW domain binding protein) Located in cytoplasmic vesicle membrane and endosome. Is integral component of organelle membrane. [provided by Alliance of Genome Resources, Apr 2022]

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_030796.5. 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
	VOPP1	NM_030796.5	MANE Select	c.211G>C	p.Val71Leu	missense	Exon 4 of 5	NP_110423.3
	VOPP1	NM_001321242.1		c.230G>C	p.Arg77Pro	missense	Exon 4 of 5	NP_001308171.1
	VOPP1	NM_001321243.2		c.98G>C	p.Arg33Pro	missense	Exon 4 of 6	NP_001308172.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VOPP1	ENST00000285279.10	TSL:1 MANE Select	c.211G>C	p.Val71Leu	missense	Exon 4 of 5	ENSP00000285279.5	Q96AW1-1
	VOPP1	ENST00000418904.5	TSL:1	c.160G>C	p.Val54Leu	missense	Exon 4 of 5	ENSP00000393210.1	Q96AW1-4
	VOPP1	ENST00000922470.1		c.211G>C	p.Val71Leu	missense	Exon 4 of 5	ENSP00000592529.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000412 AC: 1 AN: 242494 AF XY: 0.00000759

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.86e-7 AC: 1 AN: 1458672 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725278

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110558

Other (OTH) AF: 0.00 AC: 0 AN: 60252

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.9
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.24
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.39		Gain of helix (P = 0.0696)
MVP		0.44
MPC		0.78
ClinPred		0.77	D
GERP RS		4.5
Varity_R		0.22
gMVP		0.81
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs372522213; hg19: chr7-55560092;