X-47605272-C-G

Variant names:

• chrX-47605272-C-G
• NM_006950.3:c.635G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006950.3(SYN1):​c.635G>C​(p.Ser212Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,212 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: SYN1 NM_006950.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52

Genes affected

SYN1 (HGNC:11494): (synapsin I) This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. This member of the synapsin family plays a role in regulation of axonogenesis and synaptogenesis. The protein encoded serves as a substrate for several different protein kinases and phosphorylation may function in the regulation of this protein in the nerve terminal. Mutations in this gene may be associated with X-linked disorders with primary neuronal degeneration such as Rett syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ENSG00000283743 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34430814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN1	NM_006950.3	c.635G>C	p.Ser212Thr	missense_variant	Exon 4 of 13	ENST00000295987.13	NP_008881.2
SYN1	NM_133499.2	c.635G>C	p.Ser212Thr	missense_variant	Exon 4 of 13		NP_598006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN1	ENST00000295987.13	c.635G>C	p.Ser212Thr	missense_variant	Exon 4 of 13	2	NM_006950.3	ENSP00000295987.7

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096212 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 361684

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.67	D;.
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.14
Sift	Benign	0.10	T;T
Sift4G	Benign	0.081	T;T
Polyphen		0.48	P;B
Vest4		0.39
MutPred		0.74		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.34
MPC		0.96
ClinPred		0.76	D
GERP RS		5.3
Varity_R		0.49
gMVP		0.87

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-47464671;