6-83582313-A-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001242792.2(SNAP91):c.2058T>G(p.Thr686=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,613,702 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0082 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00077 (9 hom.)
• Consequence: SNAP91 NM_001242792.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.82

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 6-83582313-A-C is Benign according to our data. Variant chr6-83582313-A-C is described in ClinVar as [Benign]. Clinvar id is 787305.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.82 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00822 (1251/152226) while in subpopulation AFR AF= 0.0284 (1181/41530). AF 95% confidence interval is 0.0271. There are 14 homozygotes in gnomad4. There are 595 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP91	NM_001242792.2	c.2058T>G	p.Thr686=	synonymous_variant	23/30	ENST00000369694.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP91	ENST00000369694.7	c.2058T>G	p.Thr686=	synonymous_variant	23/30	5	NM_001242792.2	P4

Frequencies

GnomAD3 genomes AF: 0.00822 AC: 1250 AN: 152108 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00218 AC: 542 AN: 248876 Hom.: 5 AF XY: 0.00167 AC XY: 226 AN XY: 135014

Gnomad AFR exome AF: 0.0298

Gnomad AMR exome AF: 0.00183

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000976

Gnomad OTH exome AF: 0.000992

GnomAD4 exome AF: 0.000770 AC: 1125 AN: 1461476 Hom.: 9 Cov.: 31 AF XY: 0.000659 AC XY: 479 AN XY: 727006

Gnomad4 AFR exome AF: 0.0272

Gnomad4 AMR exome AF: 0.00201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000279

Gnomad4 OTH exome AF: 0.00139

GnomAD4 genome AF: 0.00822 AC: 1251 AN: 152226 Hom.: 14 Cov.: 32 AF XY: 0.00799 AC XY: 595 AN XY: 74430

Gnomad4 AFR AF: 0.0284

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00350 Hom.: 1

Bravo AF: 0.00934

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 04, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	6.3
Dann	Benign	0.63

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: rs6912747; hg19: chr6-84292032;