X-49191510-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_003179.3(SYP):c.869G>A(p.Gly290Glu) 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G290W) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 24)
• Consequence: SYP NM_003179.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.474

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant X-49191510-C-T is Benign according to our data. Variant chrX-49191510-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 130532.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYP	NM_003179.3	c.869G>A	p.Gly290Glu	missense_variant	6/7	ENST00000263233.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYP	ENST00000263233.9	c.869G>A	p.Gly290Glu	missense_variant	6/7	1	NM_003179.3	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 18, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.41	T;T
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Pathogenic	0.88	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Uncertain	0.019	D
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.79	N;N
REVEL	Uncertain	0.40
Sift	Uncertain	0.022	D;D
Sift4G	Benign	0.097	T;T
Polyphen		1.0	D;D
Vest4		0.46
MutPred		0.20		Gain of solvent accessibility (P = 0.0766);Gain of solvent accessibility (P = 0.0766);
MVP		0.80
MPC		0.58
ClinPred		0.50	D
GERP RS		4.9
Varity_R		0.21
gMVP		0.53

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

Other links and lift over

dbSNP: rs587780477; hg19: chrX-49047967;