rs6455937

Positions:

• chr6-157984277-A-C

Variant summary

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

The NM_003898.4(SYNJ2):​c.127+2189A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,194 control chromosomes in the GnomAD database, including 13,406 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 0.41 (13406 hom., cov: 34)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ2	NM_003898.4	c.127+2189A>C		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+2189A>C		intron_variant		1	NM_003898.4	ENSP00000347792.4
SYNJ2	ENST00000640338.1	c.127+2189A>C		intron_variant		1		ENSP00000492532.1
SYNJ2	ENST00000367113.5	c.49+2189A>C		intron_variant		2		ENSP00000356080.4

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62277 AN: 152076 Hom.: 13388 Cov.: 34

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.410 AC: 62343 AN: 152194 Hom.: 13406 Cov.: 34 AF XY: 0.406 AC XY: 30236 AN XY: 74418

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.385

Alfa AF: 0.414 Hom.: 1909

Bravo AF: 0.414

Asia WGS AF: 0.234 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.9
DANN	Benign	0.82

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: rs6455937; hg19: chr6-158405309;