6-158069747-C-T

Position:

• chr6-158069747-C-T

Variant summary

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

The NM_003898.4(SYNJ2):​c.1940+74C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,457,452 control chromosomes in the GnomAD database, including 96,091 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 0.36 (10313 hom., cov: 32)
  • Exomes 𝑓: 0.36 (85778 hom.)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNJ2	NM_003898.4	c.1940+74C>T		intron_variant		ENST00000355585.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ2	ENST00000355585.9	c.1940+74C>T		intron_variant		1	NM_003898.4	P2
SYNJ2	ENST00000638626.1	c.1229+74C>T		intron_variant		1
SYNJ2	ENST00000640338.1	c.1940+74C>T		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55342 AN: 151798 Hom.: 10281 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.324

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.360 AC: 469448 AN: 1305536 Hom.: 85778 AF XY: 0.361 AC XY: 230154 AN XY: 638288

Gnomad4 AFR exome AF: 0.315

Gnomad4 AMR exome AF: 0.522

Gnomad4 ASJ exome AF: 0.427

Gnomad4 EAS exome AF: 0.411

Gnomad4 SAS exome AF: 0.403

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.365 AC: 55416 AN: 151916 Hom.: 10313 Cov.: 32 AF XY: 0.365 AC XY: 27150 AN XY: 74296

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.392

Alfa AF: 0.370 Hom.: 12681

Bravo AF: 0.377

Asia WGS AF: 0.422 AC: 1471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs751873; hg19: chr6-158490779; COSMIC: COSV62897196; COSMIC: COSV62897196;