6-157997416-C-T

Variant names:

• chr6-157997416-C-T
• rs9356200
• NM_003898.4:c.127+15328C>T

Variant summary

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

The NM_003898.4(SYNJ2):​c.127+15328C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,848 control chromosomes in the GnomAD database, including 18,209 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 0.49 (18209 hom., cov: 31)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ2	NM_003898.4	c.127+15328C>T		intron_variant	Intron 1 of 26	ENST00000355585.9	NP_003889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNJ2	ENST00000355585.9	c.127+15328C>T		intron_variant	Intron 1 of 26	1	NM_003898.4	ENSP00000347792.4
SYNJ2	ENST00000640338.1	c.127+15328C>T		intron_variant	Intron 1 of 26	1		ENSP00000492532.1
SYNJ2	ENST00000367113.5	c.49+15328C>T		intron_variant	Intron 1 of 3	2		ENSP00000356080.4

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73856 AN: 151730 Hom.: 18209 Cov.: 31

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.487 AC: 73888 AN: 151848 Hom.: 18209 Cov.: 31 AF XY: 0.485 AC XY: 36016 AN XY: 74202

African (AFR) AF: 0.465 AC: 19241 AN: 41416

American (AMR) AF: 0.429 AC: 6540 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1629 AN: 3464

East Asian (EAS) AF: 0.606 AC: 3116 AN: 5140

South Asian (SAS) AF: 0.592 AC: 2844 AN: 4802

European-Finnish (FIN) AF: 0.433 AC: 4566 AN: 10534

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34373 AN: 67942

Other (OTH) AF: 0.487 AC: 1019 AN: 2094

Alfa AF: 0.498 Hom.: 11389

Bravo AF: 0.486

Asia WGS AF: 0.586 AC: 2037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.47
PhyloP100		-0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs9356200; hg19: chr6-158418448;