rs350289

chr6-158088718-A-Gchr6-158088718-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.3402A>G(p.Gly1134=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 1,613,726 control chromosomes in the GnomAD database, including 598,374 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 0.86 (57553 hom., cov: 31)
  • Exomes 𝑓: 0.86 (540821 hom.)
• Consequence: SYNJ2 NM_003898.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

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=-0.52).
• BP7: Synonymous conserved (PhyloP=-0.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNJ2	NM_003898.4	c.3402A>G	p.Gly1134=	synonymous_variant	24/27	ENST00000355585.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ2	ENST00000355585.9	c.3402A>G	p.Gly1134=	synonymous_variant	24/27	1	NM_003898.4	P2

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131286 AN: 152058 Hom.: 57510 Cov.: 31

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.861

GnomAD3 exomes AF: 0.804 AC: 201981 AN: 251232 Hom.: 84154 AF XY: 0.816 AC XY: 110843 AN XY: 135820

Gnomad AFR exome AF: 0.960

Gnomad AMR exome AF: 0.508

Gnomad ASJ exome AF: 0.915

Gnomad EAS exome AF: 0.608

Gnomad SAS exome AF: 0.841

Gnomad FIN exome AF: 0.815

Gnomad NFE exome AF: 0.880

Gnomad OTH exome AF: 0.828

GnomAD4 exome AF: 0.856 AC: 1250450 AN: 1461550 Hom.: 540821 Cov.: 53 AF XY: 0.856 AC XY: 622479 AN XY: 727112

Gnomad4 AFR exome AF: 0.965

Gnomad4 AMR exome AF: 0.523

Gnomad4 ASJ exome AF: 0.913

Gnomad4 EAS exome AF: 0.540

Gnomad4 SAS exome AF: 0.838

Gnomad4 FIN exome AF: 0.814

Gnomad4 NFE exome AF: 0.878

Gnomad4 OTH exome AF: 0.863

GnomAD4 genome AF: 0.863 AC: 131371 AN: 152176 Hom.: 57553 Cov.: 31 AF XY: 0.857 AC XY: 63702 AN XY: 74364

Gnomad4 AFR AF: 0.957

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.918

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.832

Gnomad4 FIN AF: 0.819

Gnomad4 NFE AF: 0.877

Gnomad4 OTH AF: 0.857

Alfa AF: 0.875 Hom.: 94859

Bravo AF: 0.853

Asia WGS AF: 0.729 AC: 2537 AN: 3478

EpiCase AF: 0.882

EpiControl AF: 0.887

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	4.9
Dann	Benign	0.53

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: rs350289; hg19: chr6-158509750; COSMIC: COSV62900877;