chr6-158046474-T-C

Position:

• chr6-158046474-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNJ2	NM_003898.4	c.795+3075T>C		intron_variant		ENST00000355585.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ2	ENST00000355585.9	c.795+3075T>C		intron_variant		1	NM_003898.4	P2
SYNJ2	ENST00000638626.1	c.84+3075T>C		intron_variant		1
SYNJ2	ENST00000640338.1	c.795+3075T>C		intron_variant		1		A2
SYNJ2	ENST00000485863.1	c.275+3075T>C		intron_variant, NMD_transcript_variant		3

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

Gnomad4 AFR AF: 0.0108

Gnomad4 AMR AF: 0.0320

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.0322

Gnomad4 NFE AF: 0.0561

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0491 Hom.: 90

Bravo AF: 0.0347

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.76

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: rs9295289; hg19: chr6-158467506; COSMIC: COSV62900679;