Variant chrX-49191692-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_003179.3(SYP):c.687C>T(p.Ala229=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000923 in 1,206,402 control chromosomes in the GnomAD database, including 4 homozygotes. There are 484 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., 95 hem., cov: 25)

Exomes 𝑓: 0.00078 ( 4 hom. 389 hem. )

Consequence

SYP
NM_003179.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -2.32

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant X-49191692-G-A is Benign according to our data. Variant chrX-49191692-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 198158.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2}.

BP7

Synonymous conserved (PhyloP=-2.32 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00226 (257/113504) while in subpopulation AFR AF= 0.00718 (225/31338). AF 95% confidence interval is 0.00641. There are 0 homozygotes in gnomad4. There are 95 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 95 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYP	NM_003179.3 linkuse as main transcript	c.687C>T	p.Ala229=	synonymous_variant	6/7	ENST00000263233.9	NP_003170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYP	ENST00000263233.9 linkuse as main transcript	c.687C>T	p.Ala229=	synonymous_variant	6/7	1	NM_003179.3	ENSP00000263233	P1	P08247-1

Frequencies

GnomAD3 genomes

AF:

0.00227

AC:

257

AN:

113450

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

AN XY:

35576

show subpopulations

Gnomad AFR

AF:

0.00720

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000552

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00708

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000749

Gnomad OTH

AF:

0.00131

GnomAD3 exomes

AF:

0.00180

AC:

288

AN:

159839

Hom.:

AF XY:

0.00240

AC XY:

133

AN XY:

55409

show subpopulations

Gnomad AFR exome

AF:

0.00765

Gnomad AMR exome

AF:

0.000263

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000894

Gnomad OTH exome

AF:

0.000988

GnomAD4 exome

AF:

0.000784

AC:

857

AN:

1092898

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

389

AN XY:

359602

show subpopulations

Gnomad4 AFR exome

AF:

0.00787

Gnomad4 AMR exome

AF:

0.000315

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00985

Gnomad4 FIN exome

AF:

0.000102

Gnomad4 NFE exome

AF:

0.0000679

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.00226

AC:

257

AN:

113504

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

AN XY:

35640

show subpopulations

Gnomad4 AFR

AF:

0.00718

Gnomad4 AMR

AF:

0.000551

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00711

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000749

Gnomad4 OTH

AF:

0.00129

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.00248

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 21, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jan 25, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

8.0

DANN

Benign

0.95

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