Variant 16-68862981-G-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.772G>T(p.Ala258Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000691 in 1,447,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

TANGO6
NM_024562.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.986

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:

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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=0.0972141).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TANGO6	NM_024562.2 linkuse as main transcript	c.772G>T	p.Ala258Ser	missense_variant	3/18	ENST00000261778.2	NP_078838.1	Q9C0B7B3KTB6
TANGO6	XM_047434632.1 linkuse as main transcript	c.772G>T	p.Ala258Ser	missense_variant	3/16		XP_047290588.1
TANGO6	XM_011523327.4 linkuse as main transcript	c.772G>T	p.Ala258Ser	missense_variant	3/15		XP_011521629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TANGO6	ENST00000261778.2 linkuse as main transcript	c.772G>T	p.Ala258Ser	missense_variant	3/18	1	NM_024562.2	ENSP00000261778.1	Q9C0B7
TANGO6	ENST00000561566.1 linkuse as main transcript	n.397G>T		non_coding_transcript_exon_variant	2/2	3
TANGO6	ENST00000564180.1 linkuse as main transcript	n.786G>T		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000177

AC:

AN:

225520

Hom.:

AF XY:

0.0000165

AC XY:

AN XY:

121562

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:

0.0000370

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000198

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.00000691

AC:

AN:

1447656

Hom.:

Cov.:

AF XY:

0.00000696

AC XY:

AN XY:

718440

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000509

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Alfa

AF:

0.000102

Hom.:

Asia WGS

AF:

0.00202

AC:

AN:

3478

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

Jan 29, 2024

The c.772G>T (p.A258S) alteration is located in exon 3 (coding exon 3) of the TANGO6 gene. This alteration results from a G to T substitution at nucleotide position 772, causing the alanine (A) at amino acid position 258 to be replaced by a serine (S). 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

0.092

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0076

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.090

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.63

M_CAP

Benign

0.0093

MetaRNN

Benign

0.097

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.64

REVEL

Benign

0.042

Sift

Benign

0.64

Sift4G

Benign

0.22

Polyphen

0.062

Vest4

0.19

MutPred

0.37

Gain of phosphorylation at A258 (P = 0.0207);

MVP

0.34

MPC

0.093

ClinPred

0.090

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.074

gMVP

0.16

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