X-49191592-C-T

Variant names:

• chrX-49191592-C-T
• NM_003179.3:c.787G>A

Variant summary

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

The NM_003179.3(SYP):​c.787G>A​(p.Gly263Arg) 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: 24)
• Consequence: SYP NM_003179.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73

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.787G>A	p.Gly263Arg	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.787G>A	p.Gly263Arg	missense_variant	Exon 6 of 7	1	NM_003179.3	ENSP00000263233.4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, X-linked 96 Uncertain:1

Jan 13, 2022

Revvity Omics, Revvity

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T;T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	.;T
M_CAP	Pathogenic	0.95	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Benign	0.90	L;L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.3	N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		1.0	D;D
Vest4		0.65
MutPred		0.21		Gain of solvent accessibility (P = 0.0971);Gain of solvent accessibility (P = 0.0971);
MVP		0.63
MPC		0.54
ClinPred		0.89	D
GERP RS		5.5
Varity_R		0.31
gMVP		0.52

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-49048049;