1-153658756-G-A

Position:

chr1-153658756-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012437.6(SNAPIN):c.13G>A(p.Gly5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000275 in 1,565,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

SNAPIN
NM_012437.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

SNAPIN (HGNC:17145): (SNAP associated protein) The protein encoded by this gene is a coiled-coil-forming protein that associates with the SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) complex of proteins and the BLOC-1 (biogenesis of lysosome-related organelles) complex. Biochemical studies have identified additional binding partners. As part of the SNARE complex, it is required for vesicle docking and fusion and regulates neurotransmitter release. The BLOC-1 complex is required for the biogenesis of specialized organelles such as melanosomes and platelet dense granules. Mutations in gene products that form the BLOC-1 complex have been identified in mouse strains that are models of Hermansky-Pudlak syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

SNAPIN links:

SNAPIN (HGNC:):

SNAPIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033266097).

BS2

High AC in GnomAdExome4 at 39 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAPIN	NM_012437.6 linkuse as main transcript	c.13G>A	p.Gly5Ser	missense_variant	1/4	ENST00000368685.6	NP_036569.1	O95295
SNAPIN	NR_052019.1 linkuse as main transcript	n.103G>A		non_coding_transcript_exon_variant	1/3
SNAPIN	NR_052020.1 linkuse as main transcript	n.103G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SNAPIN	ENST00000368685.6 linkuse as main transcript	c.13G>A	p.Gly5Ser	missense_variant	1/4	1	NM_012437.6	ENSP00000357674.5	O95295
SNAPIN	ENST00000462880.1 linkuse as main transcript	n.43G>A		non_coding_transcript_exon_variant	1/3	2
SNAPIN	ENST00000474959.5 linkuse as main transcript	n.45G>A		non_coding_transcript_exon_variant	1/3	2
SNAPIN	ENST00000478558.1 linkuse as main transcript	n.30G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000734

AC:

AN:

190608

Hom.:

AF XY:

0.0000560

AC XY:

AN XY:

107230

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000570

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000276

AC:

AN:

1413328

Hom.:

Cov.:

AF XY:

0.0000328

AC XY:

AN XY:

701816

show subpopulations

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:

0.000424

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.13e-7

Gnomad4 OTH exome

AF:

0.0000689

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000827

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000204

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000922

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

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 02, 2023

The c.13G>A (p.G5S) alteration is located in exon 1 (coding exon 1) of the SNAPIN gene. This alteration results from a G to A substitution at nucleotide position 13, causing the glycine (G) at amino acid position 5 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

0.080

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.094

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.71

M_CAP

Benign

0.0087

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.19

REVEL

Benign

0.070

Sift

Benign

0.19

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.19

MutPred

0.18

Gain of glycosylation at G5 (P = 0.0091);

MVP

0.54

MPC

0.54

ClinPred

0.098

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.076

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

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