NM_152906.7:c.-39-4210A>G

Variant names:

• chr22-20032550-A-G
• rs887205
• NM_152906.7:c.-39-4210A>G

Variant summary

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

The NM_152906.7(TANGO2):​c.-39-4210A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,180 control chromosomes in the GnomAD database, including 14,379 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 0.43 (14379 hom., cov: 34)
• Consequence: TANGO2 NM_152906.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANGO2	NM_152906.7	c.-39-4210A>G		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.-39-4210A>G		intron_variant	Intron 1 of 8	1	NM_152906.7	ENSP00000332721.4

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64745 AN: 152060 Hom.: 14383 Cov.: 34

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.426 AC: 64772 AN: 152180 Hom.: 14379 Cov.: 34 AF XY: 0.420 AC XY: 31252 AN XY: 74386

African (AFR) AF: 0.551 AC: 22858 AN: 41512

American (AMR) AF: 0.337 AC: 5156 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1276 AN: 3466

East Asian (EAS) AF: 0.323 AC: 1669 AN: 5174

South Asian (SAS) AF: 0.356 AC: 1721 AN: 4828

European-Finnish (FIN) AF: 0.346 AC: 3664 AN: 10592

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27202 AN: 67996

Other (OTH) AF: 0.417 AC: 881 AN: 2112

Alfa AF: 0.244 Hom.: 550

Bravo AF: 0.433

Asia WGS AF: 0.383 AC: 1337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.66
DANN	Benign	0.49
PhyloP100		-0.86
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: rs887205; hg19: chr22-20020073;