chr22-20027493-C-T

Variant names:

• chr22-20027493-C-T
• rs5748505
• NM_152906.7:c.-40+6247C>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.-40+6247C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,064 control chromosomes in the GnomAD database, including 12,100 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 0.39 (12100 hom., cov: 33)
• Consequence: TANGO2 NM_152906.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANGO2	NM_152906.7	c.-40+6247C>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.-40+6247C>T		intron_variant	Intron 1 of 8	1	NM_152906.7	ENSP00000332721.4

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59733 AN: 151946 Hom.: 12107 Cov.: 33

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.393 AC: 59748 AN: 152064 Hom.: 12100 Cov.: 33 AF XY: 0.388 AC XY: 28814 AN XY: 74342

African (AFR) AF: 0.488 AC: 20248 AN: 41470

American (AMR) AF: 0.316 AC: 4823 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1060 AN: 3468

East Asian (EAS) AF: 0.302 AC: 1565 AN: 5174

South Asian (SAS) AF: 0.277 AC: 1337 AN: 4820

European-Finnish (FIN) AF: 0.337 AC: 3564 AN: 10568

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26016 AN: 67980

Other (OTH) AF: 0.383 AC: 808 AN: 2108

Alfa AF: 0.386 Hom.: 44391

Bravo AF: 0.400

Asia WGS AF: 0.325 AC: 1132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.46
PhyloP100		-0.11
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: rs5748505; hg19: chr22-20015016;