18-9959638-T-C

Variant names:

• chr18-9959638-T-C
• rs29066
• NM_194434.3:c.*5427T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194434.3(VAPA):​c.*5427T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 149,612 control chromosomes in the GnomAD database, including 10,159 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 (10159 hom., cov: 27)
  • Failed GnomAD Quality Control
• Consequence: VAPA NM_194434.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAPA	NM_194434.3	c.*5427T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000400000.7	NP_919415.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAPA	ENST00000400000.7	c.*5427T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_194434.3	ENSP00000382880.3

Frequencies

GnomAD3 genomes AF: 0.354 AC: 52960 AN: 149506 Hom.: 10158 Cov.: 27

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.363

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.354 AC: 52960 AN: 149612 Hom.: 10159 Cov.: 27 AF XY: 0.354 AC XY: 25802 AN XY: 72894

African (AFR) AF: 0.233 AC: 9422 AN: 40430

American (AMR) AF: 0.410 AC: 6097 AN: 14888

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1556 AN: 3466

East Asian (EAS) AF: 0.117 AC: 594 AN: 5070

South Asian (SAS) AF: 0.327 AC: 1548 AN: 4740

European-Finnish (FIN) AF: 0.464 AC: 4672 AN: 10072

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27734 AN: 67666

Other (OTH) AF: 0.358 AC: 744 AN: 2076

Alfa AF: 0.398 Hom.: 14232

Bravo AF: 0.344

Asia WGS AF: 0.206 AC: 719 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.69
DANN	Benign	0.54
PhyloP100		-0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs29066; hg19: chr18-9959635;