rs3818457

Variant names:

• chr6-158077971-T-A
• rs3818457
• NM_003898.4:c.2450-193T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-158077971-T-A
• chr6-158077971-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003898.4(SYNJ2):​c.2450-193T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ2	NM_003898.4	c.2450-193T>A		intron_variant	Intron 17 of 26	ENST00000355585.9	NP_003889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNJ2	ENST00000355585.9	c.2450-193T>A		intron_variant	Intron 17 of 26	1	NM_003898.4	ENSP00000347792.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 350846 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 187786

African (AFR) AF: 0.00 AC: 0 AN: 10630

American (AMR) AF: 0.00 AC: 0 AN: 13978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10264

East Asian (EAS) AF: 0.00 AC: 0 AN: 24078

South Asian (SAS) AF: 0.00 AC: 0 AN: 39116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1436

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 208858

Other (OTH) AF: 0.00 AC: 0 AN: 19642

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.79
DANN	Benign	0.43
PhyloP100		-2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs3818457; hg19: chr6-158499003;