3-63615368-C-T

Variant names:

• chr3-63615368-C-T
• rs1284815286
• NM_001130003.2:c.745C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001130003.2(SYNPR):​c.745C>T​(p.Gln249*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000137 in 1,461,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SYNPR NM_001130003.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.84
• 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.745C>T	p.Gln249*	stop_gained	Exon 6 of 6	NP_001123475.1	Q8TBG9-2
	SYNPR	NM_144642.5		c.685C>T	p.Gln229*	stop_gained	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.745C>T	p.Gln249*	stop_gained	Exon 6 of 6	ENSP00000418994.1	Q8TBG9-2
	SYNPR	ENST00000295894.9	TSL:1	c.685C>T	p.Gln229*	stop_gained	Exon 5 of 5	ENSP00000295894.5	Q8TBG9-1
	SYNPR	ENST00000450542.6	TSL:1	c.*515C>T		3_prime_UTR	Exon 5 of 5	ENSP00000402121.2	F8WE43

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461640 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727086

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111844

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	39
DANN	Uncertain	1.0
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		4.8
Vest4		0.83
GERP RS		5.1
Mutation Taster		=47/153	disease causing

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

Other links and lift over

dbSNP: rs1284815286; hg19: chr3-63601044;