chrX-49199009-C-G

Variant names:

• chrX-49199009-C-G
• rs1165557985
• NM_003179.3:c.61G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003179.3(SYP):​c.61G>C​(p.Val21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V21M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: SYP NM_003179.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.08
• Publications: 0 publications found

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-AS1 (HGNC:40571): (SYP antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36401492).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003179.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYP	NM_003179.3	MANE Select	c.61G>C	p.Val21Leu	missense	Exon 2 of 7	NP_003170.1	P08247-1
	SYP-AS1	NR_046649.1		n.171C>G		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYP	ENST00000263233.9	TSL:1 MANE Select	c.61G>C	p.Val21Leu	missense	Exon 2 of 7	ENSP00000263233.4	P08247-1
	SYP	ENST00000479808.5	TSL:1	c.61G>C	p.Val21Leu	missense	Exon 2 of 6	ENSP00000418169.1	P08247-1
	SYP	ENST00000920145.1		c.61G>C	p.Val21Leu	missense	Exon 2 of 6	ENSP00000590204.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.1
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.31	N
REVEL	Uncertain	0.39
Sift	Benign	0.42	T
Sift4G	Benign	0.46	T
Polyphen		0.95	P
Vest4		0.34
MutPred		0.52		Loss of methylation at K23 (P = 0.1228)
MVP		0.50
MPC		1.1
ClinPred		0.85	D
GERP RS		4.3
Varity_R		0.20
gMVP		0.80
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1165557985; hg19: chrX-49055468;