rs366148

Positions:

• chr22-20054086-C-T

Variant summary

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

The ENST00000327374.9(TANGO2):​c.380+535C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0666 in 282,944 control chromosomes in the GnomAD database, including 704 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 0.061 (329 hom., cov: 33)
  • Exomes 𝑓: 0.073 (375 hom.)
• Consequence: TANGO2 ENST00000327374.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

Genes affected

TANGO2 (HGNC:25439): (transport and golgi organization 2 homolog) This gene belongs to the transport and Golgi organization family, whose members are predicted to play roles in secretory protein loading in the endoplasmic reticulum. Depletion of this gene in Drosophila S2 cells causes fusion of the Golgi with the ER. In mouse tissue culture cells, this protein co-localizes with a mitochondrially targeted mCherry protein and displays very low levels of co-localization with Golgi and peroxisomes. Allelic variants of this gene are associated with rhabdomyolysis, metabolic crises with encephalopathy, and cardiac arrhythmia. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TANGO2	NM_152906.7	c.380+535C>T		intron_variant		ENST00000327374.9	NP_690870.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TANGO2	ENST00000327374.9	c.380+535C>T		intron_variant		1	NM_152906.7	ENSP00000332721	P1

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 9312 AN: 152208 Hom.: 327 Cov.: 33

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0695

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0588

GnomAD4 exome AF: 0.0730 AC: 9535 AN: 130618 Hom.: 375 Cov.: 0 AF XY: 0.0765 AC XY: 5422 AN XY: 70838

Gnomad4 AFR exome AF: 0.0525

Gnomad4 AMR exome AF: 0.0358

Gnomad4 ASJ exome AF: 0.0802

Gnomad4 EAS exome AF: 0.0553

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.0678

Gnomad4 NFE exome AF: 0.0648

Gnomad4 OTH exome AF: 0.0737

GnomAD4 genome AF: 0.0612 AC: 9315 AN: 152326 Hom.: 329 Cov.: 33 AF XY: 0.0614 AC XY: 4575 AN XY: 74484

Gnomad4 AFR AF: 0.0572

Gnomad4 AMR AF: 0.0365

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.0565

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0695

Gnomad4 NFE AF: 0.0648

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0681 Hom.: 100

Bravo AF: 0.0567

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.63
DANN	Benign	0.48

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: rs366148; hg19: chr22-20041609;