NM_194434.3:c.417+5012T>G

Variant names:

• chr18-9942078-T-G
• rs29145
• NM_194434.3:c.417+5012T>G

Variant summary

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

The NM_194434.3(VAPA):​c.417+5012T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,126 control chromosomes in the GnomAD database, including 1,826 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 0.15 (1826 hom., cov: 32)
• Consequence: VAPA NM_194434.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAPA	NM_194434.3	c.417+5012T>G		intron_variant	Intron 4 of 5	ENST00000400000.7	NP_919415.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAPA	ENST00000400000.7	c.417+5012T>G		intron_variant	Intron 4 of 5	1	NM_194434.3	ENSP00000382880.3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23081 AN: 152008 Hom.: 1814 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0870

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.149

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.152 AC: 23114 AN: 152126 Hom.: 1826 Cov.: 32 AF XY: 0.154 AC XY: 11470 AN XY: 74366

African (AFR) AF: 0.193 AC: 7986 AN: 41452

American (AMR) AF: 0.150 AC: 2292 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0870 AC: 302 AN: 3470

East Asian (EAS) AF: 0.180 AC: 933 AN: 5176

South Asian (SAS) AF: 0.205 AC: 988 AN: 4830

European-Finnish (FIN) AF: 0.144 AC: 1531 AN: 10598

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8609 AN: 68006

Other (OTH) AF: 0.149 AC: 314 AN: 2104

Alfa AF: 0.133 Hom.: 5852

Bravo AF: 0.153

Asia WGS AF: 0.174 AC: 603 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.42
DANN	Benign	0.45
PhyloP100		-1.4
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: rs29145; hg19: chr18-9942075; COSMIC: COSV61299562;