Variant 16-68875237-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024562.2(TANGO6):c.1078T>G(p.Cys360Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000428 in 1,613,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

TANGO6
NM_024562.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.53

Variant links:

Genes affected

TANGO6 (HGNC:25749): (transport and golgi organization 6 homolog) Predicted to be involved in protein secretion. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TANGO6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TANGO6	NM_024562.2 linkuse as main transcript	c.1078T>G	p.Cys360Gly	missense_variant	5/18	ENST00000261778.2	NP_078838.1
TANGO6	XM_047434632.1 linkuse as main transcript	c.1078T>G	p.Cys360Gly	missense_variant	5/16		XP_047290588.1
TANGO6	XM_011523327.4 linkuse as main transcript	c.1078T>G	p.Cys360Gly	missense_variant	5/15		XP_011521629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TANGO6	ENST00000261778.2 linkuse as main transcript	c.1078T>G	p.Cys360Gly	missense_variant	5/18	1	NM_024562.2	ENSP00000261778	P1
TANGO6	ENST00000565852.1 linkuse as main transcript	c.16T>G	p.Cys6Gly	missense_variant, NMD_transcript_variant	1/5	4		ENSP00000462846

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000965

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

249238

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135212

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000501

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000438

AC:

AN:

1461574

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00161

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.1078T>G (p.C360G) alteration is located in exon 5 (coding exon 5) of the TANGO6 gene. This alteration results from a T to G substitution at nucleotide position 1078, causing the cysteine (C) at amino acid position 360 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.80

MetaSVM

Uncertain

0.18

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-6.8

REVEL

Pathogenic

0.78

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.84

MutPred

0.61

Gain of disorder (P = 0.0076);

MVP

0.76

MPC

0.56

ClinPred

0.67

GERP RS

4.9

Varity_R

0.73

gMVP

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over