Variant 20-1306041-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001318234.2(SNPH):c.1604G>A(p.Gly535Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000443 in 1,468,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SNPH
NM_001318234.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04874137).

BS2

High AC in GnomAd4 at 39 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNPH	NM_001318234.2 linkuse as main transcript	c.1604G>A	p.Gly535Asp	missense_variant	7/7	ENST00000381867.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNPH	ENST00000381867.6 linkuse as main transcript	c.1604G>A	p.Gly535Asp	missense_variant	7/7	1	NM_001318234.2	P3	O15079-2
SNPH	ENST00000614659.1 linkuse as main transcript	c.1604G>A	p.Gly535Asp	missense_variant	4/4	1		P3	O15079-2
SNPH	ENST00000381873.7 linkuse as main transcript	c.1472G>A	p.Gly491Asp	missense_variant	6/6	1		A1	O15079-1
SNPH	ENST00000649598.1 linkuse as main transcript	c.1571G>A	p.Gly524Asp	missense_variant	6/6			A2

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000940

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

GnomAD3 exomes

AF:

0.000124

AC:

AN:

80542

Hom.:

AF XY:

0.0000694

AC XY:

AN XY:

43244

show subpopulations

Gnomad AFR exome

AF:

0.000742

Gnomad AMR exome

AF:

0.000358

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:

0.00

Gnomad OTH exome

AF:

0.000402

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1316248

Hom.:

Cov.:

AF XY:

0.0000171

AC XY:

AN XY:

641656

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000283

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000145

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.59e-7

Gnomad4 OTH exome

AF:

0.0000733

GnomAD4 genome

AF:

0.000256

AC:

AN:

152390

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.000937

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

Alfa

AF:

0.0000869

Hom.:

Bravo

AF:

0.000212

ExAC

AF:

0.0000528

AC:

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

Sep 20, 2023

The c.1472G>A (p.G491D) alteration is located in exon 6 (coding exon 4) of the SNPH gene. This alteration results from a G to A substitution at nucleotide position 1472, causing the glycine (G) at amino acid position 491 to be replaced by an aspartic acid (D). 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

0.14

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.081

.;T;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.055

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.52

T;T;.;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.049

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.34

.;N;.;.

MutationTaster

Benign

0.93

D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.51

.;N;N;.

REVEL

Benign

0.042

Sift

Uncertain

0.015

.;D;D;.

Sift4G

Uncertain

0.046

.;D;D;D

Polyphen

0.21

.;B;B;B

Vest4

0.16, 0.17

MutPred

0.13

.;Gain of solvent accessibility (P = 0.0149);.;.;

MVP

0.082

MPC

0.64

ClinPred

0.047

GERP RS

4.9

Varity_R

0.13

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