rs12202135

Positions:

• chr6-158001048-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003898.4(SYNJ2):​c.128-16156C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,782 control chromosomes in the GnomAD database, including 1,113 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1110 hom., cov: 31)
  • Exomes 𝑓: 0.11 (3 hom.)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

Genes affected

SYNJ2 (HGNC:11504): (synaptojanin 2) The gene is a member of the inositol-polyphosphate 5-phosphatase family. The encoded protein interacts with the ras-related C3 botulinum toxin substrate 1, which causes translocation of the encoded protein to the plasma membrane where it inhibits clathrin-mediated endocytosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ2	NM_003898.4	c.128-16156C>T		intron_variant		ENST00000355585.9	NP_003889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNJ2	ENST00000355585.9	c.128-16156C>T		intron_variant		1	NM_003898.4	ENSP00000347792	P2
SYNJ2	ENST00000640338.1	c.128-16156C>T		intron_variant		1		ENSP00000492532	A2
SYNJ2	ENST00000367113.5	c.52-16156C>T		intron_variant		2		ENSP00000356080

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16268 AN: 152042 Hom.: 1114 Cov.: 31

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.106 AC: 66 AN: 624 Hom.: 3 AF XY: 0.0995 AC XY: 38 AN XY: 382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.0992

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.0500

GnomAD4 genome AF: 0.107 AC: 16254 AN: 152158 Hom.: 1110 Cov.: 31 AF XY: 0.107 AC XY: 7995 AN XY: 74386

Gnomad4 AFR AF: 0.0376

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.0916

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.112

Alfa AF: 0.132 Hom.: 1880

Bravo AF: 0.103

Asia WGS AF: 0.195 AC: 680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs12202135; hg19: chr6-158422080;