rs350292

Variant names:

• chr6-158080811-C-T
• rs350292
• NM_003898.4:c.2568-298C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003898.4(SYNJ2):​c.2568-298C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,180 control chromosomes in the GnomAD database, including 1,179 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 0.12 (1179 hom., cov: 33)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ2	NM_003898.4	c.2568-298C>T		intron_variant	Intron 18 of 26	ENST00000355585.9	NP_003889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNJ2	ENST00000355585.9	c.2568-298C>T		intron_variant	Intron 18 of 26	1	NM_003898.4	ENSP00000347792.4

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17988 AN: 152062 Hom.: 1174 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0889

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0980

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

GnomAD4 genome AF: 0.118 AC: 18008 AN: 152180 Hom.: 1179 Cov.: 33 AF XY: 0.116 AC XY: 8621 AN XY: 74380

African (AFR) AF: 0.179 AC: 7437 AN: 41508

American (AMR) AF: 0.0686 AC: 1047 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.0900 AC: 434 AN: 4824

European-Finnish (FIN) AF: 0.0931 AC: 985 AN: 10584

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7434 AN: 68020

Other (OTH) AF: 0.0984 AC: 208 AN: 2114

Alfa AF: 0.106 Hom.: 1545

Bravo AF: 0.117

Asia WGS AF: 0.0540 AC: 186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.91
DANN	Benign	0.23
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs350292; hg19: chr6-158501843;