Variant chr6-83575026-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001242792.2(SNAP91):c.2426C>T(p.Pro809Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000208 in 1,442,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SNAP91
NM_001242792.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64

Variant links:

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]

SNAP91 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16675651).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP91	NM_001242792.2 linkuse as main transcript	c.2426C>T	p.Pro809Leu	missense_variant	26/30	ENST00000369694.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP91	ENST00000369694.7 linkuse as main transcript	c.2426C>T	p.Pro809Leu	missense_variant	26/30	5	NM_001242792.2	P4	O60641-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000453

AC:

AN:

220712

Hom.:

AF XY:

0.00

AC XY:

AN XY:

118762

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000319

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1442872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715882

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000475

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.2426C>T (p.P809L) alteration is located in exon 26 (coding exon 25) of the SNAP91 gene. This alteration results from a C to T substitution at nucleotide position 2426, causing the proline (P) at amino acid position 809 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

T;T;T;T;T;.;.;.

Eigen

Benign

-0.035

Eigen_PC

Benign

0.010

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.95

.;.;D;.;D;D;D;D

M_CAP

Benign

0.0069

MetaRNN

Benign

0.17

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

.;L;.;L;L;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.0

N;N;N;N;N;N;N;N

REVEL

Benign

0.076

Sift

Benign

0.077

T;T;T;T;T;T;T;T

Sift4G

Benign

0.42

T;T;T;T;T;T;T;T

Polyphen

0.85, 0.98

.;P;.;P;P;.;D;.

Vest4

0.40

MutPred

0.24

.;Loss of glycosylation at P809 (P = 0.0236);.;Loss of glycosylation at P809 (P = 0.0236);Loss of glycosylation at P809 (P = 0.0236);.;.;.;

MVP

0.31

MPC

0.61

ClinPred

0.36

GERP RS

5.5

Varity_R

0.064

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over