6-158000656-G-C

Variant names:

• chr6-158000656-G-C
• rs7758206
• NM_003898.4:c.128-16548G>C

Variant summary

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

The NM_003898.4(SYNJ2):​c.128-16548G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,790 control chromosomes in the GnomAD database, including 11,968 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 0.35 (11968 hom., cov: 30)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354
• Publications: 1 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]

ENSG00000285642 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ2	NM_003898.4	c.128-16548G>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.128-16548G>C		intron_variant	Intron 1 of 26	1	NM_003898.4	ENSP00000347792.4
SYNJ2	ENST00000640338.1	c.128-16548G>C		intron_variant	Intron 1 of 26	1		ENSP00000492532.1
SYNJ2	ENST00000367113.5	c.50-16548G>C		intron_variant	Intron 1 of 3	2		ENSP00000356080.4
ENSG00000285642	ENST00000649179.1	n.31+63C>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53132 AN: 151672 Hom.: 11948 Cov.: 30

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.350 AC: 53193 AN: 151790 Hom.: 11968 Cov.: 30 AF XY: 0.346 AC XY: 25696 AN XY: 74162

African (AFR) AF: 0.645 AC: 26663 AN: 41340

American (AMR) AF: 0.217 AC: 3316 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 953 AN: 3472

East Asian (EAS) AF: 0.235 AC: 1214 AN: 5160

South Asian (SAS) AF: 0.325 AC: 1565 AN: 4814

European-Finnish (FIN) AF: 0.233 AC: 2458 AN: 10542

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16120 AN: 67900

Other (OTH) AF: 0.327 AC: 688 AN: 2104

Alfa AF: 0.143 Hom.: 248

Bravo AF: 0.358

Asia WGS AF: 0.284 AC: 991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.72
DANN	Benign	0.28
PhyloP100		-0.35
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: rs7758206; hg19: chr6-158421688;