chr6-83576053-T-C

Variant summary

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

The NM_001242792.2(SNAP91):ā€‹c.2300A>Gā€‹(p.Asn767Ser) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SNAP91
NM_001242792.2 missense, splice_region

Scores

2
7
10
Splicing: ADA: 0.5030
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.19
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]

Genome browser will be placed here

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 Protein UniProt
SNAP91NM_001242792.2 linkuse as main transcriptc.2300A>G p.Asn767Ser missense_variant, splice_region_variant 25/30 ENST00000369694.7 NP_001229721.1 O60641-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNAP91ENST00000369694.7 linkuse as main transcriptc.2300A>G p.Asn767Ser missense_variant, splice_region_variant 25/305 NM_001242792.2 ENSP00000358708.2 O60641-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1223448
Hom.:
0
Cov.:
19
AF XY:
0.00
AC XY:
0
AN XY:
610748
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
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.:
33

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 submitterclinical testingAmbry GeneticsAug 26, 2024The c.2300A>G (p.N767S) alteration is located in exon 25 (coding exon 24) of the SNAP91 gene. This alteration results from a A to G substitution at nucleotide position 2300, causing the asparagine (N) at amino acid position 767 to be replaced by a serine (S). 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
0.16
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T;T;T;T;T;.;.;.;.
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.92
.;.;D;.;D;D;D;D;D
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.46
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Pathogenic
3.0
.;M;.;M;M;.;.;.;.
PrimateAI
Uncertain
0.79
T
PROVEAN
Uncertain
-3.4
D;D;D;D;D;D;D;D;D
REVEL
Benign
0.17
Sift
Benign
0.033
D;D;D;D;D;D;D;D;D
Sift4G
Benign
0.10
T;T;T;T;T;T;T;D;.
Polyphen
0.87, 0.99
.;P;.;P;P;.;D;.;.
Vest4
0.73
MutPred
0.37
.;Loss of helix (P = 0.0104);.;Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);.;.;.;.;
MVP
0.62
MPC
0.52
ClinPred
0.98
D
GERP RS
5.3
Varity_R
0.26
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.50
dbscSNV1_RF
Benign
0.53
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.

Other links and lift over

dbSNP: rs994699103; hg19: chr6-84285772; API