6-158014540-A-G

Variant names:

• chr6-158014540-A-G
• rs9365723
• NM_003898.4:c.128-2664A>G

Variant summary

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

The NM_003898.4(SYNJ2):​c.128-2664A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,070 control chromosomes in the GnomAD database, including 24,746 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 0.56 (24746 hom., cov: 33)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ2	NM_003898.4	c.128-2664A>G		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.128-2664A>G		intron_variant	Intron 1 of 26	1	NM_003898.4	ENSP00000347792.4
SYNJ2	ENST00000640338.1	c.128-2664A>G		intron_variant	Intron 1 of 26	1		ENSP00000492532.1
SYNJ2	ENST00000367113.5	c.50-2664A>G		intron_variant	Intron 1 of 3	2		ENSP00000356080.4

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85681 AN: 151952 Hom.: 24740 Cov.: 33

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.564 AC: 85718 AN: 152070 Hom.: 24746 Cov.: 33 AF XY: 0.561 AC XY: 41723 AN XY: 74324

African (AFR) AF: 0.480 AC: 19900 AN: 41474

American (AMR) AF: 0.468 AC: 7157 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2529 AN: 3470

East Asian (EAS) AF: 0.475 AC: 2457 AN: 5168

South Asian (SAS) AF: 0.488 AC: 2356 AN: 4824

European-Finnish (FIN) AF: 0.597 AC: 6308 AN: 10570

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42838 AN: 67970

Other (OTH) AF: 0.594 AC: 1250 AN: 2106

Alfa AF: 0.609 Hom.: 126102

Bravo AF: 0.552

Asia WGS AF: 0.465 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.0
DANN	Benign	0.73
PhyloP100		-0.23
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)		0.040		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: rs9365723; hg19: chr6-158435572;