rs1744173

chr6-158084056-A-Gchr6-158084056-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003898.4(SYNJ2):c.3090A>G(p.Gly1030=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 1,613,910 control chromosomes in the GnomAD database, including 575,076 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 0.85 (56002 hom., cov: 31)
  • Exomes 𝑓: 0.84 (519074 hom.)
• Consequence: SYNJ2 NM_003898.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=0.148 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNJ2	NM_003898.4	c.3090A>G	p.Gly1030=	synonymous_variant	22/27	ENST00000355585.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ2	ENST00000355585.9	c.3090A>G	p.Gly1030=	synonymous_variant	22/27	1	NM_003898.4	P2

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129348 AN: 151972 Hom.: 55957 Cov.: 31

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.848

GnomAD3 exomes AF: 0.788 AC: 198244 AN: 251474 Hom.: 81090 AF XY: 0.800 AC XY: 108712 AN XY: 135906

Gnomad AFR exome AF: 0.965

Gnomad AMR exome AF: 0.501

Gnomad ASJ exome AF: 0.904

Gnomad EAS exome AF: 0.595

Gnomad SAS exome AF: 0.821

Gnomad FIN exome AF: 0.774

Gnomad NFE exome AF: 0.864

Gnomad OTH exome AF: 0.813

GnomAD4 exome AF: 0.838 AC: 1224956 AN: 1461820 Hom.: 519074 Cov.: 53 AF XY: 0.838 AC XY: 609723 AN XY: 727220

Gnomad4 AFR exome AF: 0.970

Gnomad4 AMR exome AF: 0.515

Gnomad4 ASJ exome AF: 0.901

Gnomad4 EAS exome AF: 0.531

Gnomad4 SAS exome AF: 0.818

Gnomad4 FIN exome AF: 0.774

Gnomad4 NFE exome AF: 0.860

Gnomad4 OTH exome AF: 0.847

GnomAD4 genome AF: 0.851 AC: 129434 AN: 152090 Hom.: 56002 Cov.: 31 AF XY: 0.843 AC XY: 62664 AN XY: 74324

Gnomad4 AFR AF: 0.962

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.907

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.813

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.859

Gnomad4 OTH AF: 0.844

Alfa AF: 0.867 Hom.: 88310

Bravo AF: 0.844

Asia WGS AF: 0.717 AC: 2495 AN: 3478

EpiCase AF: 0.870

EpiControl AF: 0.873

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.3
Dann	Benign	0.27

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: rs1744173; hg19: chr6-158505088; COSMIC: COSV62896085;