22-20065259-C-T

Position:

• chr22-20065259-C-T

Variant summary

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

The NM_152906.7(TANGO2):​c.*597C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,066 control chromosomes in the GnomAD database, including 15,370 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 0.44 (15367 hom., cov: 32)
  • Exomes 𝑓: 0.21 (3 hom.)
• Consequence: TANGO2 NM_152906.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813

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]

ENSG00000236540 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TANGO2	NM_152906.7	c.*597C>T		3_prime_UTR_variant	9/9	ENST00000327374.9	NP_690870.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TANGO2	ENST00000327374.9	c.*597C>T		3_prime_UTR_variant	9/9	1	NM_152906.7	ENSP00000332721.4

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66934 AN: 151760 Hom.: 15339 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.438

GnomAD4 exome AF: 0.208 AC: 40 AN: 192 Hom.: 3 Cov.: 0 AF XY: 0.200 AC XY: 18 AN XY: 90

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.417

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.441 AC: 67015 AN: 151874 Hom.: 15367 Cov.: 32 AF XY: 0.446 AC XY: 33103 AN XY: 74234

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.440

Alfa AF: 0.366 Hom.: 6603

Bravo AF: 0.454

Asia WGS AF: 0.567 AC: 1968 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	1.4
DANN	Benign	0.54

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: rs367450; hg19: chr22-20052782;