21-32678647-C-G

Variant names:

• chr21-32678647-C-G
• NM_203446.3:c.1508G>C

Variant summary

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

The NM_203446.3(SYNJ1):​c.1508G>C​(p.Arg503Pro) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000069 in 1,449,012 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SYNJ1 NM_203446.3 missense, splice_region
• Scores: Splicing: ADA: 0.9219
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.50

Genes affected

SYNJ1 (HGNC:11503): (synaptojanin 1) This gene encodes a phosphoinositide phosphatase that regulates levels of membrane phosphatidylinositol-4,5-bisphosphate. As such, expression of this enzyme may affect synaptic transmission and membrane trafficking. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

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
SYNJ1	NM_203446.3	c.1508G>C	p.Arg503Pro	missense_variant, splice_region_variant	Exon 12 of 33	ENST00000674351.1	NP_982271.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNJ1	ENST00000674351.1	c.1508G>C	p.Arg503Pro	missense_variant, splice_region_variant	Exon 12 of 33		NM_203446.3	ENSP00000501530.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449012 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 720758

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	.;T;.;T;T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D
M_CAP	Benign	0.0084	T
MetaRNN	Uncertain	0.49	T;D;D;T;T;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;.;.;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.7	N;N;.;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.18	T;T;.;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T;.
Polyphen		0.99	D;.;.;P;.;.
Vest4		0.64
MutPred		0.42		Gain of sheet (P = 0.0101);.;.;.;.;.;
MVP		0.49
MPC		1.8
ClinPred		0.92	D
GERP RS		5.7
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.92
dbscSNV1_RF	Benign	0.66
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: chr21-34050957;