rs29067

Positions:

• chr18-9957921-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194434.3(VAPA):​c.*3710T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,138 control chromosomes in the GnomAD database, including 9,925 homozygotes. 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: 𝑓 0.35 (9925 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VAPA NM_194434.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134

Genes affected

VAPA (HGNC:12648): (VAMP associated protein A) The protein encoded by this gene is a type IV membrane protein. It is present in the plasma membrane and intracellular vesicles. It may also be associated with the cytoskeleton. This protein may function in vesicle trafficking, membrane fusion, protein complex assembly and cell motility. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAPA	NM_194434.3	c.*3710T>G		3_prime_UTR_variant	6/6	ENST00000400000.7	NP_919415.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAPA	ENST00000400000.7	c.*3710T>G		3_prime_UTR_variant	6/6	1	NM_194434.3	ENSP00000382880.3

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52704 AN: 152020 Hom.: 9924 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.352

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.346 AC: 52704 AN: 152138 Hom.: 9925 Cov.: 33 AF XY: 0.346 AC XY: 25765 AN XY: 74364

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.348

Alfa AF: 0.388 Hom.: 23048

Bravo AF: 0.338

Asia WGS AF: 0.204 AC: 711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.69

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: rs29067; hg19: chr18-9957918;