6-157994577-A-T

Position:

• chr6-157994577-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003898.4(SYNJ2):​c.127+12489A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,078 control chromosomes in the GnomAD database, including 11,792 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 0.37 (11792 hom., cov: 32)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ2	NM_003898.4	c.127+12489A>T		intron_variant		ENST00000355585.9	NP_003889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNJ2	ENST00000355585.9	c.127+12489A>T		intron_variant		1	NM_003898.4	ENSP00000347792.4
SYNJ2	ENST00000640338.1	c.127+12489A>T		intron_variant		1		ENSP00000492532.1
SYNJ2	ENST00000367113.5	c.49+12489A>T		intron_variant		2		ENSP00000356080.4

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55931 AN: 151960 Hom.: 11764 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.368 AC: 56002 AN: 152078 Hom.: 11792 Cov.: 32 AF XY: 0.363 AC XY: 27007 AN XY: 74338

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.330

Alfa AF: 0.207 Hom.: 450

Bravo AF: 0.377

Asia WGS AF: 0.234 AC: 814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.38
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs6906464; hg19: chr6-158415609;