Variant chr6-83575057-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001242792.2(SNAP91):c.2395G>C(p.Val799Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SNAP91
NM_001242792.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP91	NM_001242792.2 linkuse as main transcript	c.2395G>C	p.Val799Leu	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.2395G>C	p.Val799Leu	missense_variant	26/30	5	NM_001242792.2	P4	O60641-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000125

Hom.:

Bravo

AF:

0.0000189

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

Nov 21, 2023

The c.2395G>C (p.V799L) alteration is located in exon 26 (coding exon 25) of the SNAP91 gene. This alteration results from a G to C substitution at nucleotide position 2395, causing the valine (V) at amino acid position 799 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

Pathogenic

0.64

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

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

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

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

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.46

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

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.7

.;M;.;M;M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;N;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.6

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

REVEL

Benign

0.23

Sift

Uncertain

0.012

D;D;D;D;D;D;T;D

Sift4G

Benign

0.11

T;T;T;T;T;T;T;D

Polyphen

0.97, 0.97

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

Vest4

0.65

MutPred

0.20

.;Loss of methylation at K798 (P = 0.0545);.;Loss of methylation at K798 (P = 0.0545);Loss of methylation at K798 (P = 0.0545);.;.;.;

MVP

0.61

MPC

0.55

ClinPred

0.92

GERP RS

5.8

Varity_R

0.22

gMVP

0.37

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