6-83678457-T-C

Position:

• chr6-83678457-T-C

Variant summary

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

The NM_001242792.2(SNAP91):​c.131-12876A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,066 control chromosomes in the GnomAD database, including 4,289 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 0.21 (4289 hom., cov: 32)
• Consequence: SNAP91 NM_001242792.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP91	NM_001242792.2	c.131-12876A>G		intron_variant		ENST00000369694.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP91	ENST00000369694.7	c.131-12876A>G		intron_variant		5	NM_001242792.2	P4

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32433 AN: 151948 Hom.: 4279 Cov.: 32

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.213 AC: 32450 AN: 152066 Hom.: 4289 Cov.: 32 AF XY: 0.217 AC XY: 16144 AN XY: 74328

Gnomad4 AFR AF: 0.0608

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.234

Alfa AF: 0.225 Hom.: 625

Bravo AF: 0.213

Asia WGS AF: 0.274 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.066
DANN	Benign	0.50

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: rs755101; hg19: chr6-84388176;