3-63615248-C-G

Variant names:

• chr3-63615248-C-G
• NM_001130003.2:c.625C>G

Variant summary

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

The NM_001130003.2(SYNPR):​c.625C>G​(p.Leu209Val) variant causes a missense change involving the alteration of a 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: 33)
• Consequence: SYNPR NM_001130003.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

Genes affected

SYNPR (HGNC:16507): (synaptoporin) Predicted to be located in neuron projection and synaptic vesicle. Predicted to be integral component of membrane. Predicted to be active in synaptic vesicle membrane. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

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
SYNPR	NM_001130003.2	c.625C>G	p.Leu209Val	missense_variant	Exon 6 of 6	ENST00000478300.6	NP_001123475.1
SYNPR	NM_144642.5	c.565C>G	p.Leu189Val	missense_variant	Exon 5 of 5		NP_653243.1
SYNPR	XM_017005731.1	c.673C>G	p.Leu225Val	missense_variant	Exon 6 of 6		XP_016861220.1
SYNPR	XM_017005732.3	c.*4706C>G		downstream_gene_variant			XP_016861221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNPR	ENST00000478300.6	c.625C>G	p.Leu209Val	missense_variant	Exon 6 of 6	1	NM_001130003.2	ENSP00000418994.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.625C>G (p.L209V) alteration is located in exon 6 (coding exon 6) of the SYNPR gene. This alteration results from a C to G substitution at nucleotide position 625, causing the leucine (L) at amino acid position 209 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	.;T;T;.
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.3	.;M;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.4	N;N;N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Benign	0.080	T;T;T;D
Polyphen		1.0	.;D;D;.
Vest4		0.72
MutPred		0.78		.;.;Gain of catalytic residue at L200 (P = 0.0265);.;
MVP		0.28
MPC		0.39
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.63
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr3-63600924;