chr6-157989345-A-C

Variant names:

• chr6-157989345-A-C
• rs7772395
• NM_003898.4:c.127+7257A>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.127+7257A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 150,006 control chromosomes in the GnomAD database, including 3,801 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 0.21 (3801 hom., cov: 29)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003898.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2	NM_003898.4	MANE Select	c.127+7257A>C		intron	N/A	NP_003889.1
	SYNJ2	NM_001410947.1		c.127+7257A>C		intron	N/A	NP_001397876.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2	ENST00000355585.9	TSL:1 MANE Select	c.127+7257A>C		intron	N/A	ENSP00000347792.4
	SYNJ2	ENST00000640338.1	TSL:1	c.127+7257A>C		intron	N/A	ENSP00000492532.1
	SYNJ2	ENST00000367113.5	TSL:2	c.49+7257A>C		intron	N/A	ENSP00000356080.4

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32222 AN: 149904 Hom.: 3799 Cov.: 29

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.0172

Gnomad SAS AF: 0.0923

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.215 AC: 32246 AN: 150006 Hom.: 3801 Cov.: 29 AF XY: 0.213 AC XY: 15576 AN XY: 73138

African (AFR) AF: 0.288 AC: 11757 AN: 40818

American (AMR) AF: 0.152 AC: 2288 AN: 15088

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 702 AN: 3458

East Asian (EAS) AF: 0.0172 AC: 88 AN: 5118

South Asian (SAS) AF: 0.0933 AC: 441 AN: 4728

European-Finnish (FIN) AF: 0.213 AC: 2126 AN: 9986

Middle Eastern (MID) AF: 0.287 AC: 82 AN: 286

European-Non Finnish (NFE) AF: 0.211 AC: 14263 AN: 67552

Other (OTH) AF: 0.194 AC: 402 AN: 2068

Alfa AF: 0.214 Hom.: 8194

Bravo AF: 0.217

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.59
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: rs7772395; hg19: chr6-158410377;