6-158094079-C-T

Position:

• chr6-158094079-C-T

Variant summary

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

The ENST00000640338.1(SYNJ2):​c.*69C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 723,194 control chromosomes in the GnomAD database, including 19,893 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 0.18 (3128 hom., cov: 31)
  • Exomes 𝑓: 0.23 (16765 hom.)
• Consequence: SYNJ2 ENST00000640338.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNJ2	NM_003898.4	c.3744+975C>T		intron_variant		ENST00000355585.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ2	ENST00000355585.9	c.3744+975C>T		intron_variant		1	NM_003898.4	P2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28055 AN: 151928 Hom.: 3131 Cov.: 31

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.229 AC: 130954 AN: 571148 Hom.: 16765 Cov.: 0 AF XY: 0.235 AC XY: 72584 AN XY: 309212

Gnomad4 AFR exome AF: 0.0701

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.350

Gnomad4 EAS exome AF: 0.00636

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.184 AC: 28051 AN: 152046 Hom.: 3128 Cov.: 31 AF XY: 0.181 AC XY: 13461 AN XY: 74324

Gnomad4 AFR AF: 0.0683

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.0130

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.219

Alfa AF: 0.221 Hom.: 1921

Bravo AF: 0.181

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.64

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: rs13217929; hg19: chr6-158515111;