7-55497685-C-G

Variant names:

• chr7-55497685-C-G
• rs1259687008
• NM_030796.5:c.119G>C

Variant summary

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

The NM_030796.5(VOPP1):​c.119G>C​(p.Arg40Pro) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R40L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VOPP1 NM_030796.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.08

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

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 rank	MANE	Protein	UniProt
VOPP1	NM_030796.5	c.119G>C	p.Arg40Pro	missense_variant	Exon 3 of 5	ENST00000285279.10	NP_110423.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VOPP1	ENST00000285279.10	c.119G>C	p.Arg40Pro	missense_variant	Exon 3 of 5	1	NM_030796.5	ENSP00000285279.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.;.;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.71	D;D;D;D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.1	M;.;.;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.6	D;D;.;D;D
REVEL	Uncertain	0.32
Sift	Benign	0.17	T;T;.;T;T
Sift4G	Uncertain	0.0040	D;D;D;D;D
Polyphen		1.0	D;.;.;.;.
Vest4		0.86
MutPred		0.36		Gain of loop (P = 0.1069);.;.;.;.;
MVP		0.19
MPC		0.95
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.52
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1259687008; hg19: chr7-55565378;