Variant 16-68860121-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024562.2(TANGO6):c.332G>A(p.Arg111His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00097 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 0 hom. )

Consequence

TANGO6
NM_024562.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.12

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0057534575).

BP6

Variant 16-68860121-G-A is Benign according to our data. Variant chr16-68860121-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3324366.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TANGO6	NM_024562.2 linkuse as main transcript	c.332G>A	p.Arg111His	missense_variant	2/18	ENST00000261778.2	NP_078838.1
TANGO6	XM_047434632.1 linkuse as main transcript	c.332G>A	p.Arg111His	missense_variant	2/16		XP_047290588.1
TANGO6	XM_011523327.4 linkuse as main transcript	c.332G>A	p.Arg111His	missense_variant	2/15		XP_011521629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TANGO6	ENST00000261778.2 linkuse as main transcript	c.332G>A	p.Arg111His	missense_variant	2/18	1	NM_024562.2	ENSP00000261778	P1
TANGO6	ENST00000564180.1 linkuse as main transcript	n.346G>A		non_coding_transcript_exon_variant	2/4	2
TANGO6	ENST00000561566.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000973

AC:

148

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00109

AC:

271

AN:

249244

Hom.:

AF XY:

0.00111

AC XY:

150

AN XY:

135210

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00201

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.00166

AC:

2422

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1185

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.00206

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.000972

AC:

148

AN:

152246

Hom.:

Cov.:

AF XY:

0.000887

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00159

Hom.:

Bravo

AF:

0.000994

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00128

AC:

ESP6500EA

AF:

0.00193

AC:

ExAC

AF:

0.00117

AC:

141

EpiCase

AF:

0.00147

EpiControl

AF:

0.00196

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 07, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.97

DANN

Benign

0.37

DEOGEN2

Benign

0.0060

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.57

M_CAP

Benign

0.0029

MetaRNN

Benign

0.0058

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.58

REVEL

Benign

0.028

Sift

Benign

0.42

Sift4G

Benign

0.25

Polyphen

0.0010

Vest4

0.014

MVP

0.048

MPC

0.12

ClinPred

0.0015

GERP RS

-10

Varity_R

0.015

gMVP

0.097

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