6-158094079-C-T

Variant names:

• chr6-158094079-C-T
• rs13217929
• ENST00000640338.1:c.*69C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.8).
• 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 rank	MANE	Protein	UniProt
SYNJ2	NM_003898.4	c.3744+975C>T		intron_variant	Intron 26 of 26	ENST00000355585.9	NP_003889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNJ2	ENST00000355585.9	c.3744+975C>T		intron_variant	Intron 26 of 26	1	NM_003898.4	ENSP00000347792.4

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

African (AFR) AF: 0.0701 AC: 1146 AN: 16346

American (AMR) AF: 0.150 AC: 5842 AN: 39058

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 6809 AN: 19470

East Asian (EAS) AF: 0.00636 AC: 222 AN: 34926

South Asian (SAS) AF: 0.236 AC: 15043 AN: 63648

European-Finnish (FIN) AF: 0.172 AC: 6339 AN: 36776

Middle Eastern (MID) AF: 0.382 AC: 1374 AN: 3594

European-Non Finnish (NFE) AF: 0.266 AC: 86934 AN: 326234

Other (OTH) AF: 0.233 AC: 7245 AN: 31096

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

African (AFR) AF: 0.0683 AC: 2833 AN: 41486

American (AMR) AF: 0.186 AC: 2847 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1207 AN: 3472

East Asian (EAS) AF: 0.0130 AC: 67 AN: 5170

South Asian (SAS) AF: 0.215 AC: 1034 AN: 4804

European-Finnish (FIN) AF: 0.170 AC: 1798 AN: 10578

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.257 AC: 17450 AN: 67958

Other (OTH) AF: 0.219 AC: 460 AN: 2100

Alfa AF: 0.225 Hom.: 2183

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
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13217929; hg19: chr6-158515111;