6-83660150-T-C

Variant names:

• chr6-83660150-T-C
• rs217308
• NM_001242792.2:c.453-1058A>G

Variant summary

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

The NM_001242792.2(SNAP91):​c.453-1058A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,012 control chromosomes in the GnomAD database, including 11,656 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 0.38 (11656 hom., cov: 32)
• Consequence: SNAP91 NM_001242792.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242792.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP91	NM_001242792.2	MANE Select	c.453-1058A>G		intron	N/A	NP_001229721.1	O60641-1
	SNAP91	NM_014841.3		c.453-1058A>G		intron	N/A	NP_055656.1	O60641-1
	SNAP91	NM_001376675.1		c.453-1058A>G		intron	N/A	NP_001363604.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP91	ENST00000369694.7	TSL:5 MANE Select	c.453-1058A>G		intron	N/A	ENSP00000358708.2	O60641-1
	SNAP91	ENST00000520302.5	TSL:1	c.453-1058A>G		intron	N/A	ENSP00000428511.1	O60641-4
	SNAP91	ENST00000520213.5	TSL:1	c.453-1058A>G		intron	N/A	ENSP00000428026.1	O60641-3

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58284 AN: 151894 Hom.: 11651 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.384 AC: 58302 AN: 152012 Hom.: 11656 Cov.: 32 AF XY: 0.386 AC XY: 28686 AN XY: 74272

African (AFR) AF: 0.269 AC: 11136 AN: 41454

American (AMR) AF: 0.371 AC: 5667 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2169 AN: 5162

South Asian (SAS) AF: 0.502 AC: 2417 AN: 4816

European-Finnish (FIN) AF: 0.480 AC: 5062 AN: 10536

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29514 AN: 67972

Other (OTH) AF: 0.365 AC: 771 AN: 2112

Alfa AF: 0.397 Hom.: 15869

Bravo AF: 0.368

Asia WGS AF: 0.477 AC: 1657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.55
PhyloP100		-0.56
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs217308;

hg19: chr6-84369869;