6-83582258-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001242792.2(SNAP91):c.2113C>T(p.Pro705Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000799 in 1,613,570 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (5 hom.)
• Consequence: SNAP91 NM_001242792.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.23

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008294463).
• BP6: Variant 6-83582258-G-A is Benign according to our data. Variant chr6-83582258-G-A is described in ClinVar as [Benign]. Clinvar id is 737562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP91	NM_001242792.2	c.2113C>T	p.Pro705Ser	missense_variant	23/30	ENST00000369694.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP91	ENST00000369694.7	c.2113C>T	p.Pro705Ser	missense_variant	23/30	5	NM_001242792.2	P4

Frequencies

GnomAD3 genomes AF: 0.00397 AC: 604 AN: 151984 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00230

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00384

GnomAD3 exomes AF: 0.00128 AC: 320 AN: 249034 Hom.: 2 AF XY: 0.000984 AC XY: 133 AN XY: 135094

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000975

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.000468 AC: 684 AN: 1461468 Hom.: 5 Cov.: 31 AF XY: 0.000385 AC XY: 280 AN XY: 727020

Gnomad4 AFR exome AF: 0.0135

Gnomad4 AMR exome AF: 0.00170

Gnomad4 ASJ exome AF: 0.00134

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000486

Gnomad4 OTH exome AF: 0.000994

GnomAD4 genome AF: 0.00398 AC: 606 AN: 152102 Hom.: 3 Cov.: 32 AF XY: 0.00375 AC XY: 279 AN XY: 74374

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.0226 Hom.: 2347

Bravo AF: 0.00453

ESP6500AA AF: 0.0124 AC: 49

ESP6500EA AF: 0.000240 AC: 2

ExAC AF: 0.00147 AC: 178

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000356

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

Apr 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.45
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.020	T;T;T;T;T;.;.;.;.
Eigen	Benign	0.015
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.89	D
MetaRNN	Benign	0.0083	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.1	N;N;N;N;N;N;N;D;N
REVEL	Benign	0.044
Sift	Benign	0.077	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.16	T;T;T;T;T;T;T;T;.
Polyphen		0.21, 0.95	.;B;.;B;B;.;P;.;.
Vest4		0.39
MVP		0.33
MPC		0.60
ClinPred		0.013	T
GERP RS		5.4
Varity_R		0.092
gMVP		0.45

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: rs61729902; hg19: chr6-84291977; COSMIC: COSV104561293; COSMIC: COSV104561293;