Variant 20-1300587-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001318234.2(SNPH):c.316A>T(p.Ser106Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

SNPH
NM_001318234.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.22

Variant links:

Genes affected

SNPH (HGNC:15931): (syntaphilin) Syntaxin-1, synaptobrevin/VAMP, and SNAP25 interact to form the SNARE complex, which is required for synaptic vesicle docking and fusion. The protein encoded by this gene is membrane-associated and inhibits SNARE complex formation by binding free syntaxin-1. Expression of this gene appears to be brain-specific. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

SNPH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27081963).

BS2

High AC in GnomAdExome4 at 59 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNPH	NM_001318234.2 linkuse as main transcript	c.316A>T	p.Ser106Cys	missense_variant	6/7	ENST00000381867.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNPH	ENST00000381867.6 linkuse as main transcript	c.316A>T	p.Ser106Cys	missense_variant	6/7	1	NM_001318234.2	P3	O15079-2
SNPH	ENST00000614659.1 linkuse as main transcript	c.316A>T	p.Ser106Cys	missense_variant	3/4	1		P3	O15079-2
SNPH	ENST00000381873.7 linkuse as main transcript	c.184A>T	p.Ser62Cys	missense_variant	5/6	1		A1	O15079-1
SNPH	ENST00000649598.1 linkuse as main transcript	c.283A>T	p.Ser95Cys	missense_variant	5/6			A2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152196

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000400

AC:

AN:

250162

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135340

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000404

AC:

AN:

1461638

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000513

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74346

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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 08, 2022

The c.184A>T (p.S62C) alteration is located in exon 5 (coding exon 3) of the SNPH gene. This alteration results from a A to T substitution at nucleotide position 184, causing the serine (S) at amino acid position 62 to be replaced by a cysteine (C). 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

0.19

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

.;D;.;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

D;D;.;D

M_CAP

Benign

0.0070

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

2.0

.;M;.;.

MutationTaster

Benign

0.57

N;N

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.6

.;D;D;.

REVEL

Benign

0.17

Sift

Uncertain

0.0040

.;D;D;.

Sift4G

Uncertain

0.019

.;D;D;D

Polyphen

1.0

.;D;D;D

Vest4

0.63, 0.61, 0.62

MVP

0.20

MPC

1.4

ClinPred

0.44

GERP RS

5.0

Varity_R

0.18

gMVP

0.59

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