3-63278729-G-A

Position:

• chr3-63278729-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001130003.2(SYNPR):​c.71G>A​(p.Arg24Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYNPR NM_001130003.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.74

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNPR	NM_001130003.2	c.71G>A	p.Arg24Gln	missense_variant	2/6	ENST00000478300.6	NP_001123475.1
SYNPR	XM_017005732.3	c.71G>A	p.Arg24Gln	missense_variant	2/6		XP_016861221.1
SYNPR	XM_017005731.1	c.132+26143G>A		intron_variant			XP_016861220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNPR	ENST00000478300.6	c.71G>A	p.Arg24Gln	missense_variant	2/6	1	NM_001130003.2	ENSP00000418994	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 12, 2023

The c.71G>A (p.R24Q) alteration is located in exon 2 (coding exon 2) of the SYNPR gene. This alteration results from a G to A substitution at nucleotide position 71, causing the arginine (R) at amino acid position 24 to be replaced by a glutamine (Q). 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
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	27
DANN	Pathogenic	1.0
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.92	D;T
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.3	N;D
REVEL	Benign	0.20
Sift	Uncertain	0.0060	D;.
Sift4G	Uncertain	0.014	D;D
Vest4		0.66
MutPred		0.72		Loss of methylation at R24 (P = 0.0429);Loss of methylation at R24 (P = 0.0429);
MVP		0.48
MPC		0.40
ClinPred		0.96	D
GERP RS		5.2
gMVP		0.83

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: chr3-63264405;