chr6-158084056-A-G

Variant names:

• chr6-158084056-A-G
• rs1744173
• NM_003898.4:c.3090A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003898.4(SYNJ2):​c.3090A>G​(p.Gly1030Gly) 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
• Publications: 22 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 -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.

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.3090A>G	p.Gly1030Gly	synonymous	Exon 22 of 27	NP_003889.1
	SYNJ2	NM_001410947.1		c.3090A>G	p.Gly1030Gly	synonymous	Exon 22 of 28	NP_001397876.1
	SYNJ2	NM_001178088.2		c.2379A>G	p.Gly793Gly	synonymous	Exon 21 of 26	NP_001171559.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2	ENST00000355585.9	TSL:1 MANE Select	c.3090A>G	p.Gly1030Gly	synonymous	Exon 22 of 27	ENSP00000347792.4
	SYNJ2	ENST00000640338.1	TSL:1	c.3090A>G	p.Gly1030Gly	synonymous	Exon 22 of 27	ENSP00000492532.1
	SYNJ2	ENST00000638626.1	TSL:1	c.2379A>G	p.Gly793Gly	synonymous	Exon 21 of 26	ENSP00000492369.1

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

GnomAD2 exomes AF: 0.788 AC: 198244 AN: 251474 AF XY: 0.800

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 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

African (AFR) AF: 0.970 AC: 32467 AN: 33480

American (AMR) AF: 0.515 AC: 23040 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 23556 AN: 26136

East Asian (EAS) AF: 0.531 AC: 21061 AN: 39696

South Asian (SAS) AF: 0.818 AC: 70580 AN: 86258

European-Finnish (FIN) AF: 0.774 AC: 41355 AN: 53418

Middle Eastern (MID) AF: 0.913 AC: 5265 AN: 5768

European-Non Finnish (NFE) AF: 0.860 AC: 956505 AN: 1111944

Other (OTH) AF: 0.847 AC: 51127 AN: 60396

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

African (AFR) AF: 0.962 AC: 39931 AN: 41516

American (AMR) AF: 0.647 AC: 9875 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3148 AN: 3472

East Asian (EAS) AF: 0.587 AC: 3029 AN: 5156

South Asian (SAS) AF: 0.813 AC: 3909 AN: 4810

European-Finnish (FIN) AF: 0.776 AC: 8204 AN: 10570

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58421 AN: 67982

Other (OTH) AF: 0.844 AC: 1780 AN: 2108

Alfa AF: 0.865 Hom.: 108409

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.27
PhyloP100		0.15
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: rs1744173; hg19: chr6-158505088; COSMIC: COSV62896085;