chr6-157991466-G-A

Position:

• chr6-157991466-G-A

Variant summary

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

The NM_003898.4(SYNJ2):​c.127+9378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,938 control chromosomes in the GnomAD database, including 21,016 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 0.51 (21016 hom., cov: 31)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNJ2	NM_003898.4	c.127+9378G>A		intron_variant		ENST00000355585.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ2	ENST00000355585.9	c.127+9378G>A		intron_variant		1	NM_003898.4	P2
SYNJ2	ENST00000640338.1	c.127+9378G>A		intron_variant		1		A2
SYNJ2	ENST00000367113.5	c.51+9378G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77004 AN: 151820 Hom.: 20988 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.507 AC: 77082 AN: 151938 Hom.: 21016 Cov.: 31 AF XY: 0.505 AC XY: 37492 AN XY: 74238

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.481

Alfa AF: 0.449 Hom.: 3163

Bravo AF: 0.519

Asia WGS AF: 0.506 AC: 1759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.8
DANN	Benign	0.89

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: rs10455935; hg19: chr6-158412498;