Variant 1-153659495-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_012437.6(SNAPIN):c.238C>G(p.Pro80Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,974 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)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SNAPIN
NM_012437.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.00

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:

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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	Protein	UniProt
SNAPIN	NM_012437.6 linkuse as main transcript	c.238C>G	p.Pro80Ala	missense_variant	3/4	ENST00000368685.6	NP_036569.1	O95295
SNAPIN	NR_052019.1 linkuse as main transcript	n.281C>G		non_coding_transcript_exon_variant	2/3
SNAPIN	NR_052020.1 linkuse as main transcript	n.267C>G		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SNAPIN	ENST00000368685.6 linkuse as main transcript	c.238C>G	p.Pro80Ala	missense_variant	3/4	1	NM_012437.6	ENSP00000357674.5	O95295
SNAPIN	ENST00000462880.1 linkuse as main transcript	n.221C>G		non_coding_transcript_exon_variant	2/3	2
SNAPIN	ENST00000474959.5 linkuse as main transcript	n.521C>G		non_coding_transcript_exon_variant	2/3	2
SNAPIN	ENST00000478558.1 linkuse as main transcript	n.769C>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

AF:

0.00000205

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

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

AF:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

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

Bravo

AF:

0.0000113

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 07, 2023

The c.238C>G (p.P80A) alteration is located in exon 3 (coding exon 3) of the SNAPIN gene. This alteration results from a C to G substitution at nucleotide position 238, causing the proline (P) at amino acid position 80 to be replaced by an alanine (A). 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

Uncertain

0.52

BayesDel_addAF

Uncertain

0.078

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Benign

0.81

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0091

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.1

REVEL

Benign

0.19

Sift

Benign

0.60

Sift4G

Benign

1.0

Polyphen

0.60

Vest4

0.81

MutPred

0.61

Loss of loop (P = 0.0128);

MVP

0.67

MPC

0.60

ClinPred

0.65

GERP RS

5.6

Varity_R

0.16

gMVP

0.52

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