rs10455936

Positions:

• chr6-157991487-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003898.4(SYNJ2):​c.127+9399C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,030 control chromosomes in the GnomAD database, including 4,539 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 0.24 (4539 hom., cov: 32)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

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 (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ2	NM_003898.4	c.127+9399C>T		intron_variant		ENST00000355585.9	NP_003889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNJ2	ENST00000355585.9	c.127+9399C>T		intron_variant		1	NM_003898.4	ENSP00000347792	P2
SYNJ2	ENST00000640338.1	c.127+9399C>T		intron_variant		1		ENSP00000492532	A2
SYNJ2	ENST00000367113.5	c.51+9399C>T		intron_variant		2		ENSP00000356080

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36242 AN: 151912 Hom.: 4531 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.239 AC: 36263 AN: 152030 Hom.: 4539 Cov.: 32 AF XY: 0.240 AC XY: 17816 AN XY: 74296

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.239

Alfa AF: 0.231 Hom.: 5524

Bravo AF: 0.241

Asia WGS AF: 0.418 AC: 1452 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	8.4
DANN	Benign	0.85

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: rs10455936; hg19: chr6-158412519; COSMIC: COSV62896243;