Variant 16-68860166-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024562.2(TANGO6):c.377C>T(p.Pro126Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TANGO6
NM_024562.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.38

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:

TANGO6 (HGNC:):

TANGO6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22488704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TANGO6	NM_024562.2 linkuse as main transcript	c.377C>T	p.Pro126Leu	missense_variant	2/18	ENST00000261778.2	NP_078838.1	Q9C0B7B3KTB6
TANGO6	XM_047434632.1 linkuse as main transcript	c.377C>T	p.Pro126Leu	missense_variant	2/16		XP_047290588.1
TANGO6	XM_011523327.4 linkuse as main transcript	c.377C>T	p.Pro126Leu	missense_variant	2/15		XP_011521629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TANGO6	ENST00000261778.2 linkuse as main transcript	c.377C>T	p.Pro126Leu	missense_variant	2/18	1	NM_024562.2	ENSP00000261778.1	Q9C0B7
TANGO6	ENST00000561566.1 linkuse as main transcript	n.2C>T		non_coding_transcript_exon_variant	1/2	3
TANGO6	ENST00000564180.1 linkuse as main transcript	n.391C>T		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249246

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135210

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

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

Nov 24, 2024

The c.377C>T (p.P126L) alteration is located in exon 2 (coding exon 2) of the TANGO6 gene. This alteration results from a C to T substitution at nucleotide position 377, causing the proline (P) at amino acid position 126 to be replaced by a leucine (L). 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

Benign

0.10

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.021

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.15

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.013

Polyphen

1.0

Vest4

0.19

MVP

0.23

MPC

0.38

ClinPred

0.93

GERP RS

5.4

Varity_R

0.14

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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