6-83600212-A-T

Variant names:

• chr6-83600212-A-T
• rs9294279
• NM_001242792.2:c.1324+1059T>A

Variant summary

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

The NM_001242792.2(SNAP91):​c.1324+1059T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,134 control chromosomes in the GnomAD database, including 45,900 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 0.77 (45900 hom., cov: 32)
• Consequence: SNAP91 NM_001242792.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 2 publications found

Genes affected

SNAP91 (HGNC:14986): (synaptosome associated protein 91) Predicted to enable several functions, including SNARE binding activity; clathrin binding activity; and phosphatidylinositol binding activity. Acts upstream of or within regulation of clathrin-dependent endocytosis. Predicted to be located in several cellular components, including postsynaptic density; presynaptic endosome; and presynaptic membrane. Predicted to be extrinsic component of endosome membrane. Predicted to be active in several cellular components, including Schaffer collateral - CA1 synapse; cytoplasmic vesicle; and parallel fiber to Purkinje cell synapse. Predicted to be extrinsic component of presynaptic endocytic zone membrane. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP91	NM_001242792.2	c.1324+1059T>A		intron_variant	Intron 16 of 29	ENST00000369694.7	NP_001229721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP91	ENST00000369694.7	c.1324+1059T>A		intron_variant	Intron 16 of 29	5	NM_001242792.2	ENSP00000358708.2

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117453 AN: 152016 Hom.: 45827 Cov.: 32

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.773 AC: 117589 AN: 152134 Hom.: 45900 Cov.: 32 AF XY: 0.776 AC XY: 57718 AN XY: 74350

African (AFR) AF: 0.868 AC: 36029 AN: 41520

American (AMR) AF: 0.791 AC: 12096 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2215 AN: 3472

East Asian (EAS) AF: 0.878 AC: 4538 AN: 5168

South Asian (SAS) AF: 0.830 AC: 4000 AN: 4822

European-Finnish (FIN) AF: 0.754 AC: 7980 AN: 10580

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48438 AN: 67970

Other (OTH) AF: 0.739 AC: 1560 AN: 2110

Alfa AF: 0.751 Hom.: 5379

Bravo AF: 0.775

Asia WGS AF: 0.839 AC: 2918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.017
DANN	Benign	0.37
PhyloP100		-1.5
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: rs9294279; hg19: chr6-84309931;