7-55472989-G-T

Position:

• chr7-55472989-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_030796.5(VOPP1):​c.385C>A​(p.Pro129Thr) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VOPP1 NM_030796.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20013541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VOPP1	NM_030796.5	c.385C>A	p.Pro129Thr	missense_variant	5/5	ENST00000285279.10	NP_110423.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VOPP1	ENST00000285279.10	c.385C>A	p.Pro129Thr	missense_variant	5/5	1	NM_030796.5	ENSP00000285279	P1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000208 AC: 3 AN: 1442642 Hom.: 0 Cov.: 30 AF XY: 0.00000279 AC XY: 2 AN XY: 717558

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000272

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2023

The c.385C>A (p.P129T) alteration is located in exon 5 (coding exon 5) of the VOPP1 gene. This alteration results from a C to A substitution at nucleotide position 385, causing the proline (P) at amino acid position 129 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T;.;.;.;.;.;.;.;.;.;.
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;D;.;.;D;D;D;D;D;D;D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.0	L;.;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	0.67	D;D;D;D;D;D;D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.5	D;D;D;D;.;D;D;D;D;D;D
REVEL	Benign	0.12
Sift	Benign	0.21	T;T;D;D;.;T;T;D;T;D;D
Sift4G	Uncertain	0.019	D;D;D;D;D;D;.;D;D;D;.
Polyphen		0.97	D;.;.;.;.;.;.;.;.;.;.
Vest4		0.25
MutPred		0.33		Gain of glycosylation at P129 (P = 0.0447);.;.;.;.;.;.;.;.;.;.;
MVP		0.19
MPC		0.83
ClinPred		0.86	D
GERP RS		4.7
Varity_R		0.18
gMVP		0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs1791944935; hg19: chr7-55540682;