6-157998349-T-A

Variant names:

• chr6-157998349-T-A
• rs9456954
• NM_003898.4:c.127+16261T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 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.127+16261T>A		intron	N/A	NP_003889.1
	SYNJ2	NM_001410947.1		c.127+16261T>A		intron	N/A	NP_001397876.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2	ENST00000355585.9	TSL:1 MANE Select	c.127+16261T>A		intron	N/A	ENSP00000347792.4
	SYNJ2	ENST00000640338.1	TSL:1	c.127+16261T>A		intron	N/A	ENSP00000492532.1
	SYNJ2	ENST00000367113.5	TSL:2	c.49+16261T>A		intron	N/A	ENSP00000356080.4

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

African (AFR) AF: 0.652 AC: 27052 AN: 41472

American (AMR) AF: 0.310 AC: 4742 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1093 AN: 3472

East Asian (EAS) AF: 0.377 AC: 1947 AN: 5166

South Asian (SAS) AF: 0.399 AC: 1925 AN: 4820

European-Finnish (FIN) AF: 0.310 AC: 3284 AN: 10582

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22432 AN: 67992

Other (OTH) AF: 0.390 AC: 824 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.73
DANN	Benign	0.89
PhyloP100		-0.69
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: rs9456954; hg19: chr6-158419381;