6-83560882-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001242792.2(SNAP91):c.2508T>C(p.Pro836=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00589 in 1,613,732 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (35 hom.)
• Consequence: SNAP91 NM_001242792.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.568

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 6-83560882-A-G is Benign according to our data. Variant chr6-83560882-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 778343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.568 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP91	NM_001242792.2	c.2508T>C	p.Pro836=	synonymous_variant	27/30	ENST00000369694.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP91	ENST00000369694.7	c.2508T>C	p.Pro836=	synonymous_variant	27/30	5	NM_001242792.2	P4

Frequencies

GnomAD3 genomes AF: 0.00438 AC: 667 AN: 152164 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00622

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00679

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00458 AC: 1139 AN: 248842 Hom.: 5 AF XY: 0.00439 AC XY: 592 AN XY: 134982

Gnomad AFR exome AF: 0.000775

Gnomad AMR exome AF: 0.00227

Gnomad ASJ exome AF: 0.000597

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000884

Gnomad FIN exome AF: 0.00659

Gnomad NFE exome AF: 0.00743

Gnomad OTH exome AF: 0.00597

GnomAD4 exome AF: 0.00605 AC: 8838 AN: 1461450 Hom.: 35 Cov.: 30 AF XY: 0.00594 AC XY: 4316 AN XY: 726996

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.00246

Gnomad4 ASJ exome AF: 0.000421

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000905

Gnomad4 FIN exome AF: 0.00659

Gnomad4 NFE exome AF: 0.00712

Gnomad4 OTH exome AF: 0.00510

GnomAD4 genome AF: 0.00437 AC: 666 AN: 152282 Hom.: 1 Cov.: 33 AF XY: 0.00416 AC XY: 310 AN XY: 74470

Gnomad4 AFR AF: 0.00125

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00622

Gnomad4 NFE AF: 0.00679

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00566 Hom.: 0

Bravo AF: 0.00441

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00567

EpiControl AF: 0.00765

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 20, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2022	SNAP91: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	6.2
Dann	Benign	0.44

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: rs12208676; hg19: chr6-84270601;