rs350292

chr6-158080811-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.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

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=-0.96).
• 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/exons	MANE	UniProt
SYNJ2	NM_003898.4	c.2568-298C>T		intron_variant		ENST00000355585.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ2	ENST00000355585.9	c.2568-298C>T		intron_variant		1	NM_003898.4	P2

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

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0900

Gnomad4 FIN AF: 0.0931

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0984

Alfa AF: 0.105 Hom.: 1202

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs350292; hg19: chr6-158501843;