18-9957921-T-G

Variant names:

• chr18-9957921-T-G
• rs29067
• NM_194434.3:c.*3710T>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.*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
• Publications: 12 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194434.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAPA	NM_194434.3	MANE Select	c.*3710T>G		3_prime_UTR	Exon 6 of 6	NP_919415.2
	VAPA	NM_003574.6		c.*3710T>G		3_prime_UTR	Exon 7 of 7	NP_003565.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAPA	ENST00000400000.7	TSL:1 MANE Select	c.*3710T>G		3_prime_UTR	Exon 6 of 6	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

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) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.232 AC: 9629 AN: 41532

American (AMR) AF: 0.401 AC: 6126 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1540 AN: 3470

East Asian (EAS) AF: 0.109 AC: 565 AN: 5184

South Asian (SAS) AF: 0.323 AC: 1558 AN: 4820

European-Finnish (FIN) AF: 0.457 AC: 4818 AN: 10546

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27144 AN: 67976

Other (OTH) AF: 0.348 AC: 734 AN: 2110

Alfa AF: 0.379 Hom.: 46420

Bravo AF: 0.338

Asia WGS AF: 0.204 AC: 711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.69
PhyloP100		0.13
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: rs29067; hg19: chr18-9957918;