7-55497633-T-C

Variant names:

• chr7-55497633-T-C
• rs750529839
• NM_030796.5:c.171A>G

Variant summary

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

The NM_030796.5(VOPP1):​c.171A>G​(p.Ile57Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000647 in 1,607,944 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I57L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: VOPP1 NM_030796.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0500
• 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.171A>G	p.Ile57Met	missense	Exon 3 of 5	NP_110423.3
	VOPP1	NM_001321242.1		c.190A>G	p.Thr64Ala	missense	Exon 3 of 5	NP_001308171.1
	VOPP1	NM_001321243.2		c.58A>G	p.Thr20Ala	missense	Exon 3 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.171A>G	p.Ile57Met	missense	Exon 3 of 5	ENSP00000285279.5	Q96AW1-1
	VOPP1	ENST00000418904.5	TSL:1	c.120A>G	p.Ile40Met	missense	Exon 3 of 5	ENSP00000393210.1	Q96AW1-4
	VOPP1	ENST00000428097.5	TSL:3	c.-31A>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 5	ENSP00000389601.1	C9JIM1

Frequencies

GnomAD3 genomes AF: 0.0000337 AC: 5 AN: 148538 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000746

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000281 AC: 7 AN: 249080 AF XY: 0.0000296

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000678 AC: 99 AN: 1459406 Hom.: 0 Cov.: 34 AF XY: 0.0000565 AC XY: 41 AN XY: 726030

African (AFR) AF: 0.000120 AC: 4 AN: 33434

American (AMR) AF: 0.0000224 AC: 1 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39458

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.0000810 AC: 90 AN: 1110480

Other (OTH) AF: 0.0000664 AC: 4 AN: 60248

GnomAD4 genome AF: 0.0000337 AC: 5 AN: 148538 Hom.: 0 Cov.: 32 AF XY: 0.0000416 AC XY: 3 AN XY: 72102

African (AFR) AF: 0.0000746 AC: 3 AN: 40204

American (AMR) AF: 0.00 AC: 0 AN: 14866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 4916

South Asian (SAS) AF: 0.00 AC: 0 AN: 4682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67476

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.000119 Hom.: 0

ExAC AF: 0.00000826 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.050
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.87
MVP		0.099
MPC		0.78
ClinPred		0.33	T
GERP RS		-9.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.18
gMVP		0.77
Mutation Taster		=65/35	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: rs750529839; hg19: chr7-55565326; COSMIC: COSV99567281;