Variant chr20-1304951-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001318234.2(SNPH):c.514C>T(p.Arg172Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SNPH
NM_001318234.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06

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 -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.805

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNPH	NM_001318234.2 linkuse as main transcript	c.514C>T	p.Arg172Cys	missense_variant	7/7	ENST00000381867.6	NP_001305163.1	O15079-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SNPH	ENST00000381867.6 linkuse as main transcript	c.514C>T	p.Arg172Cys	missense_variant	7/7	1	NM_001318234.2	ENSP00000371291.1	O15079-2
SNPH	ENST00000614659.1 linkuse as main transcript	c.514C>T	p.Arg172Cys	missense_variant	4/4	1		ENSP00000479696.1	O15079-2
SNPH	ENST00000381873.7 linkuse as main transcript	c.382C>T	p.Arg128Cys	missense_variant	6/6	1		ENSP00000371297.3	O15079-1
SNPH	ENST00000649598.1 linkuse as main transcript	c.481C>T	p.Arg161Cys	missense_variant	6/6			ENSP00000496966.1	A0A3B3IRY9

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152170

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251322

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461532

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74330

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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 04, 2024

The c.382C>T (p.R128C) alteration is located in exon 6 (coding exon 4) of the SNPH gene. This alteration results from a C to T substitution at nucleotide position 382, causing the arginine (R) at amino acid position 128 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

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.82

.;D;.;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.98

D;D;.;D

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.80

D;D;D;D

MetaSVM

Uncertain

0.31

MutationAssessor

Uncertain

2.9

.;M;.;.

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-6.5

.;D;D;.

REVEL

Uncertain

0.62

Sift

Pathogenic

0.0

.;D;D;.

Sift4G

Pathogenic

0.0

.;D;D;D

Polyphen

1.0

.;D;D;D

Vest4

0.84, 0.85

MutPred

0.23

.;Loss of disorder (P = 0.0619);.;.;

MVP

0.49

MPC

1.7

ClinPred

1.0

GERP RS

4.6

Varity_R

0.67

gMVP

0.75

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