chr3-63615248-C-G

Variant names:

• chr3-63615248-C-G
• rs1025615820
• NM_001130003.2:c.625C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

SYNPR-AS1 (HGNC:40774): (SYNPR antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130003.2. 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
	SYNPR	NM_001130003.2	MANE Select	c.625C>G	p.Leu209Val	missense	Exon 6 of 6	NP_001123475.1	Q8TBG9-2
	SYNPR	NM_144642.5		c.565C>G	p.Leu189Val	missense	Exon 5 of 5	NP_653243.1	Q8TBG9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPR	ENST00000478300.6	TSL:1 MANE Select	c.625C>G	p.Leu209Val	missense	Exon 6 of 6	ENSP00000418994.1	Q8TBG9-2
	SYNPR	ENST00000295894.9	TSL:1	c.565C>G	p.Leu189Val	missense	Exon 5 of 5	ENSP00000295894.5	Q8TBG9-1
	SYNPR	ENST00000450542.6	TSL:1	c.*395C>G		3_prime_UTR	Exon 5 of 5	ENSP00000402121.2	F8WE43

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.78
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.080	T
Polyphen		1.0	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
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs1025615820; hg19: chr3-63600924;