Variant X-49191477-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003179.3(SYP):c.902G>A(p.Gly301Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000354 in 113,061 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., 0 hem., cov: 24)

Consequence

SYP
NM_003179.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.80

Variant links:

Genes affected

SYP (HGNC:11506): (synaptophysin) This gene encodes an integral membrane protein of small synaptic vesicles in brain and endocrine cells. The protein also binds cholesterol and is thought to direct targeting of vesicle-associated membrane protein 2 (synaptobrevin) to intracellular compartments. Mutations in this gene are associated with an X-linked form of cognitive disability. [provided by RefSeq, Jul 2017]

SYP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27345017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYP	NM_003179.3 link	c.902G>A	p.Gly301Asp	missense_variant	Exon 6 of 7	ENST00000263233.9	NP_003170.1	P08247-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYP	ENST00000263233.9 link	c.902G>A	p.Gly301Asp	missense_variant	Exon 6 of 7	1	NM_003179.3	ENSP00000263233.4		P08247-1

Frequencies

GnomAD3 genomes

AF:

0.0000354

AC:

AN:

113061

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35197

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:

0.0000750

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000354

AC:

AN:

113061

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35197

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:

0.0000750

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jan 21, 2022

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;T

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.83

.;T

M_CAP

Pathogenic

0.74

MetaRNN

Benign

0.27

T;T

MetaSVM

Uncertain

0.093

MutationAssessor

Benign

0.97

L;L

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.70

N;N

REVEL

Benign

0.24

Sift

Benign

0.25

T;T

Sift4G

Benign

0.60

T;T

Polyphen

0.0020

B;B

Vest4

0.22

MVP

0.57

MPC

0.59

ClinPred

0.55

GERP RS

5.5

Varity_R

0.18

gMVP

0.42

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