rs887205

Positions:

• chr22-20032550-A-G
• chr22-20032550-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• 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/exons	MANE	UniProt
TANGO2	NM_152906.7	c.-39-4210A>G		intron_variant		ENST00000327374.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TANGO2	ENST00000327374.9	c.-39-4210A>G		intron_variant		1	NM_152906.7	P1

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

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.417

Alfa AF: 0.221 Hom.: 430

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

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: rs887205; hg19: chr22-20020073;