NM_003898.4:c.128-13543T>C

Variant names:

• chr6-158003661-T-C
• rs9459093
• NM_003898.4:c.128-13543T>C

Variant summary

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

The NM_003898.4(SYNJ2):​c.128-13543T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 152,026 control chromosomes in the GnomAD database, including 21,801 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 0.51 (21801 hom., cov: 32)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ2	NM_003898.4	c.128-13543T>C		intron_variant	Intron 1 of 26	ENST00000355585.9	NP_003889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNJ2	ENST00000355585.9	c.128-13543T>C		intron_variant	Intron 1 of 26	1	NM_003898.4	ENSP00000347792.4
SYNJ2	ENST00000640338.1	c.128-13543T>C		intron_variant	Intron 1 of 26	1		ENSP00000492532.1
SYNJ2	ENST00000367113.5	c.50-13543T>C		intron_variant	Intron 1 of 3	2		ENSP00000356080.4

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78131 AN: 151908 Hom.: 21760 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.500

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.515 AC: 78220 AN: 152026 Hom.: 21801 Cov.: 32 AF XY: 0.508 AC XY: 37754 AN XY: 74288

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.497

Alfa AF: 0.442 Hom.: 29467

Bravo AF: 0.526

Asia WGS AF: 0.430 AC: 1494 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.62

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: rs9459093; hg19: chr6-158424693;