NM_001130003.2:c.19C>A

Variant names:

• chr3-63278677-C-A
• rs571542496
• NM_001130003.2:c.19C>A

Variant summary

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

The NM_001130003.2(SYNPR):​c.19C>A​(p.Leu7Met) variant causes a missense, splice region 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. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L7L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYNPR NM_001130003.2 missense, splice_region
• Scores: Splicing: ADA: 0.002953
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• 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]

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=0.27317357).

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.19C>A	p.Leu7Met	missense splice_region	Exon 2 of 6	NP_001123475.1	Q8TBG9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPR	ENST00000478300.6	TSL:1 MANE Select	c.19C>A	p.Leu7Met	missense splice_region	Exon 2 of 6	ENSP00000418994.1	Q8TBG9-2
	SYNPR	ENST00000450542.6	TSL:1	c.19C>A	p.Leu7Met	missense splice_region	Exon 2 of 5	ENSP00000402121.2	F8WE43
	SYNPR	ENST00000460142.6	TSL:4	n.12C>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	23
DANN	Uncertain	0.99
Eigen	Benign	0.15
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.0
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.070
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.25	T
Vest4		0.47
MutPred		0.22		Gain of glycosylation at T12 (P = 0.0591)
MVP		0.28
MPC		0.34
ClinPred		0.93	D
GERP RS		4.3
PromoterAI		0.27	Neutral
gMVP		0.58
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0030
dbscSNV1_RF	Benign	0.14
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: rs571542496; hg19: chr3-63264353;