rs9456954

Positions:

• chr6-157998349-T-A
• chr6-157998349-T-C
• chr6-157998349-T-G

Variant summary

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

The NM_003898.4(SYNJ2):​c.127+16261T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,116 control chromosomes in the GnomAD database, including 14,938 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 0.42 (14938 hom., cov: 33)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNJ2	NM_003898.4	c.127+16261T>A		intron_variant		ENST00000355585.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ2	ENST00000355585.9	c.127+16261T>A		intron_variant		1	NM_003898.4	P2
SYNJ2	ENST00000640338.1	c.127+16261T>A		intron_variant		1		A2
SYNJ2	ENST00000367113.5	c.51+16261T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63544 AN: 151998 Hom.: 14917 Cov.: 33

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.418 AC: 63603 AN: 152116 Hom.: 14938 Cov.: 33 AF XY: 0.415 AC XY: 30874 AN XY: 74366

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.390

Alfa AF: 0.236 Hom.: 529

Bravo AF: 0.426

Asia WGS AF: 0.388 AC: 1350 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.73
DANN	Benign	0.89

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: rs9456954; hg19: chr6-158419381;