chr6-83560902-C-T

Position:

• chr6-83560902-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001242792.2(SNAP91):​c.2488G>A​(p.Ala830Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SNAP91 NM_001242792.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84

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 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=0.1421063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP91	NM_001242792.2	c.2488G>A	p.Ala830Thr	missense_variant	27/30	ENST00000369694.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP91	ENST00000369694.7	c.2488G>A	p.Ala830Thr	missense_variant	27/30	5	NM_001242792.2	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461262 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 726898

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2023

The c.2488G>A (p.A830T) alteration is located in exon 27 (coding exon 26) of the SNAP91 gene. This alteration results from a G to A substitution at nucleotide position 2488, causing the alanine (A) at amino acid position 830 to be replaced by a threonine (T). 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	0.061
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T;T;T;T;T;.;.;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	.;.;T;.;D;D;D;D
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	.;L;.;L;L;.;.;.
MutationTaster	Benign	0.99	D;D;D;D;D;D;D;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.65	N;N;N;N;N;N;N;N
REVEL	Benign	0.047
Sift	Benign	0.39	T;T;T;T;T;T;T;T
Sift4G	Benign	0.49	T;T;T;T;T;T;T;T
Polyphen		0.0040, 0.11	.;B;.;B;B;.;B;.
Vest4		0.40
MutPred		0.14		.;Gain of glycosylation at A830 (P = 0.0019);.;Gain of glycosylation at A830 (P = 0.0019);Gain of glycosylation at A830 (P = 0.0019);.;.;.;
MVP		0.39
MPC		0.58
ClinPred		0.64	D
GERP RS		4.8
Varity_R		0.074
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-84270621;