X-155239176-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003372.7(VBP1):c.*334T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: VBP1 NM_003372.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498

Genes affected

VBP1 (HGNC:12662): (VHL binding protein 1) The protein encoded by this gene interacts with the Von Hippel-Lindau protein to form an intracellular complex. The encoded protein functions as a chaperone protein, and may play a role in the transport of the Von Hippel-Lindau protein from the perinuclear granules to the nucleus or cytoplasm. Alternative splicing and the use of alternate transcription start sites results in multiple transcript variants encoding different protein isoforms. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VBP1	NM_003372.7	c.*334T>G		3_prime_UTR_variant	6/6	ENST00000286428.7
VBP1	NM_001303543.1	c.*334T>G		3_prime_UTR_variant	6/6
VBP1	NM_001303544.1	c.*334T>G		3_prime_UTR_variant	7/7
VBP1	NM_001303545.1	c.*334T>G		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VBP1	ENST00000286428.7	c.*334T>G		3_prime_UTR_variant	6/6	1	NM_003372.7	P1
VBP1	ENST00000625964.2	c.*334T>G		3_prime_UTR_variant	6/6	5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.9

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: rs11887; hg19: chrX-154467457;