rs1744169

Positions:

• chr6-158087193-A-G
• chr6-158087193-A-T

Variant summary

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

The NM_003898.4(SYNJ2):​c.3343+204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,096 control chromosomes in the GnomAD database, including 36,600 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 0.68 (36600 hom., cov: 32)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNJ2	NM_003898.4	c.3343+204A>G		intron_variant		ENST00000355585.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ2	ENST00000355585.9	c.3343+204A>G		intron_variant		1	NM_003898.4	P2

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103371 AN: 151980 Hom.: 36555 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.680 AC: 103458 AN: 152096 Hom.: 36600 Cov.: 32 AF XY: 0.676 AC XY: 50254 AN XY: 74326

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.637

Alfa AF: 0.631 Hom.: 13797

Bravo AF: 0.673

Asia WGS AF: 0.624 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.89
DANN	Benign	0.19

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: rs1744169; hg19: chr6-158508225; COSMIC: COSV62900391;