chr6-158046474-T-C

Variant names:

• chr6-158046474-T-C
• rs9295289
• NM_003898.4:c.795+3075T>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.795+3075T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 152,314 control chromosomes in the GnomAD database, including 128 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 0.035 (128 hom., cov: 32)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0546 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.795+3075T>C		intron	N/A	NP_003889.1
	SYNJ2	NM_001410947.1		c.795+3075T>C		intron	N/A	NP_001397876.1
	SYNJ2	NM_001178088.2		c.84+3075T>C		intron	N/A	NP_001171559.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2	ENST00000355585.9	TSL:1 MANE Select	c.795+3075T>C		intron	N/A	ENSP00000347792.4
	SYNJ2	ENST00000640338.1	TSL:1	c.795+3075T>C		intron	N/A	ENSP00000492532.1
	SYNJ2	ENST00000638626.1	TSL:1	c.84+3075T>C		intron	N/A	ENSP00000492369.1

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5347 AN: 152196 Hom.: 128 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.0244

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

GnomAD4 genome AF: 0.0351 AC: 5346 AN: 152314 Hom.: 128 Cov.: 32 AF XY: 0.0340 AC XY: 2535 AN XY: 74482

African (AFR) AF: 0.0108 AC: 450 AN: 41562

American (AMR) AF: 0.0320 AC: 490 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4822

European-Finnish (FIN) AF: 0.0322 AC: 342 AN: 10624

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0561 AC: 3817 AN: 68022

Other (OTH) AF: 0.0241 AC: 51 AN: 2116

Alfa AF: 0.0488 Hom.: 133

Bravo AF: 0.0347

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.76
PhyloP100		-0.31
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: rs9295289; hg19: chr6-158467506; COSMIC: COSV62900679;