6-158088718-A-G

Variant names:

• chr6-158088718-A-G
• rs350289
• NM_003898.4:c.3402A>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.3402A>G​(p.Gly1134Gly) 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. Synonymous variant affecting the same amino acid position (i.e. G1134G) has been classified as Uncertain significance.

• 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
• Publications: 23 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=-0.52).
• 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2	NM_003898.4	MANE Select	c.3402A>G	p.Gly1134Gly	synonymous	Exon 24 of 27	NP_003889.1	O15056-1
	SYNJ2	NM_001410947.1		c.3402A>G	p.Gly1134Gly	synonymous	Exon 24 of 28	NP_001397876.1	O15056-3
	SYNJ2	NM_001178088.2		c.2691A>G	p.Gly897Gly	synonymous	Exon 23 of 26	NP_001171559.1	A0A1W2PR85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2	ENST00000355585.9	TSL:1 MANE Select	c.3402A>G	p.Gly1134Gly	synonymous	Exon 24 of 27	ENSP00000347792.4	O15056-1
	SYNJ2	ENST00000640338.1	TSL:1	c.3402A>G	p.Gly1134Gly	synonymous	Exon 24 of 27	ENSP00000492532.1	O15056-3
	SYNJ2	ENST00000638626.1	TSL:1	c.2691A>G	p.Gly897Gly	synonymous	Exon 23 of 26	ENSP00000492369.1	A0A1W2PR85

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

GnomAD2 exomes AF: 0.804 AC: 201981 AN: 251232 AF XY: 0.816

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 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

African (AFR) AF: 0.965 AC: 32303 AN: 33472

American (AMR) AF: 0.523 AC: 23380 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 23860 AN: 26134

East Asian (EAS) AF: 0.540 AC: 21437 AN: 39672

South Asian (SAS) AF: 0.838 AC: 72266 AN: 86232

European-Finnish (FIN) AF: 0.814 AC: 43429 AN: 53340

Middle Eastern (MID) AF: 0.917 AC: 5286 AN: 5766

European-Non Finnish (NFE) AF: 0.878 AC: 976379 AN: 1111844

Other (OTH) AF: 0.863 AC: 52110 AN: 60386

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

African (AFR) AF: 0.957 AC: 39752 AN: 41538

American (AMR) AF: 0.659 AC: 10068 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3186 AN: 3470

East Asian (EAS) AF: 0.601 AC: 3103 AN: 5164

South Asian (SAS) AF: 0.832 AC: 4010 AN: 4822

European-Finnish (FIN) AF: 0.819 AC: 8666 AN: 10578

Middle Eastern (MID) AF: 0.918 AC: 268 AN: 292

European-Non Finnish (NFE) AF: 0.877 AC: 59629 AN: 68012

Other (OTH) AF: 0.857 AC: 1809 AN: 2110

Alfa AF: 0.871 Hom.: 124267

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	4.9
DANN	Benign	0.53
PhyloP100		-0.22
Mutation Taster		=91/9	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: rs350289; hg19: chr6-158509750; COSMIC: COSV62900877;