NM_003898.4:c.214+1835G>A

Variant names:

• chr6-158019125-G-A
• rs10046389
• NM_003898.4:c.214+1835G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003898.4(SYNJ2):​c.214+1835G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,186 control chromosomes in the GnomAD database, including 11,778 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 0.39 (11778 hom., cov: 34)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 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.214+1835G>A		intron	N/A	NP_003889.1
	SYNJ2	NM_001410947.1		c.214+1835G>A		intron	N/A	NP_001397876.1
	SYNJ2	NM_001178088.2		c.-498+1835G>A		intron	N/A	NP_001171559.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2	ENST00000355585.9	TSL:1 MANE Select	c.214+1835G>A		intron	N/A	ENSP00000347792.4
	SYNJ2	ENST00000640338.1	TSL:1	c.214+1835G>A		intron	N/A	ENSP00000492532.1
	SYNJ2	ENST00000638626.1	TSL:1	c.-498+1835G>A		intron	N/A	ENSP00000492369.1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 59065 AN: 152068 Hom.: 11763 Cov.: 34

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.388 AC: 59115 AN: 152186 Hom.: 11778 Cov.: 34 AF XY: 0.384 AC XY: 28577 AN XY: 74412

African (AFR) AF: 0.414 AC: 17192 AN: 41524

American (AMR) AF: 0.321 AC: 4906 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1306 AN: 5166

South Asian (SAS) AF: 0.321 AC: 1548 AN: 4826

European-Finnish (FIN) AF: 0.350 AC: 3708 AN: 10600

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27807 AN: 67992

Other (OTH) AF: 0.394 AC: 833 AN: 2112

Alfa AF: 0.394 Hom.: 1503

Bravo AF: 0.389

Asia WGS AF: 0.303 AC: 1052 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.70
PhyloP100		0.14
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: rs10046389; hg19: chr6-158440157;