X-49191493-C-T

Variant names:

• chrX-49191493-C-T
• NM_003179.3:c.886G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003179.3(SYP):​c.886G>A​(p.Gly296Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 25)
• Consequence: SYP NM_003179.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYP	NM_003179.3	c.886G>A	p.Gly296Arg	missense_variant	Exon 6 of 7	ENST00000263233.9	NP_003170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYP	ENST00000263233.9	c.886G>A	p.Gly296Arg	missense_variant	Exon 6 of 7	1	NM_003179.3	ENSP00000263233.4

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Oct 02, 2019

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this 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	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	.;T
M_CAP	Pathogenic	0.73	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.39
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.84	P;P
Vest4		0.52
MutPred		0.20		Gain of solvent accessibility (P = 0.1319);Gain of solvent accessibility (P = 0.1319);
MVP		0.68
MPC		0.54
ClinPred		0.83	D
GERP RS		4.3
Varity_R		0.32
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-49047950;