rs6518598

Variant names:

• chr22-20034415-G-T
• rs6518598
• NM_152906.7:c.-39-2345G>T

Variant summary

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

The NM_152906.7(TANGO2):​c.-39-2345G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,058 control chromosomes in the GnomAD database, including 7,664 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 0.30 (7664 hom., cov: 33)
• Consequence: TANGO2 NM_152906.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 5 publications found

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]

TANGO2 Gene-Disease associations (from GenCC):

• recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

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 = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANGO2	NM_152906.7	c.-39-2345G>T		intron_variant	Intron 1 of 8	ENST00000327374.9	NP_690870.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANGO2	ENST00000327374.9	c.-39-2345G>T		intron_variant	Intron 1 of 8	1	NM_152906.7	ENSP00000332721.4

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46364 AN: 151940 Hom.: 7672 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.305 AC: 46352 AN: 152058 Hom.: 7664 Cov.: 33 AF XY: 0.302 AC XY: 22457 AN XY: 74326

African (AFR) AF: 0.181 AC: 7506 AN: 41486

American (AMR) AF: 0.282 AC: 4314 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3470

East Asian (EAS) AF: 0.312 AC: 1618 AN: 5182

South Asian (SAS) AF: 0.274 AC: 1322 AN: 4822

European-Finnish (FIN) AF: 0.344 AC: 3626 AN: 10550

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25925 AN: 67960

Other (OTH) AF: 0.320 AC: 675 AN: 2112

Alfa AF: 0.346 Hom.: 5275

Bravo AF: 0.299

Asia WGS AF: 0.307 AC: 1069 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	0.18
DANN	Benign	0.79
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6518598; hg19: chr22-20021938;