rs149152116

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000425018.1(TUBGCP6):c.1165C>T(p.Arg389Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,612,482 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R389H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 11 hom. )

Consequence

TUBGCP6
ENST00000425018.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.308

Variant links:

Genes affected

TUBGCP6 (HGNC:18127): (tubulin gamma complex component 6) The protein encoded by this gene is part of a large multisubunit complex required for microtubule nucleation at the centrosome. [provided by RefSeq, Jul 2008]

TUBGCP6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009924054).

BP6

Variant 22-50218218-G-A is Benign according to our data. Variant chr22-50218218-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 437142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50218218-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00204 (311/152320) while in subpopulation NFE AF= 0.00347 (236/68020). AF 95% confidence interval is 0.00311. There are 2 homozygotes in gnomad4. There are 142 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP6	NM_020461.4 link	c.5139C>T	p.His1713His	synonymous_variant	Exon 23 of 25	ENST00000248846.10	NP_065194.3	Q96RT7-1
TUBGCP6	XR_938347.3 link	n.*78C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10 link	c.5139C>T	p.His1713His	synonymous_variant	Exon 23 of 25	1	NM_020461.4	ENSP00000248846.5		Q96RT7-1

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

311

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00347

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00210

AC:

523

AN:

249006

Hom.:

AF XY:

0.00217

AC XY:

293

AN XY:

135040

show subpopulations

Gnomad AFR exome

AF:

0.000870

Gnomad AMR exome

AF:

0.00148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00216

Gnomad FIN exome

AF:

0.000380

Gnomad NFE exome

AF:

0.00329

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.00325

AC:

4743

AN:

1460162

Hom.:

Cov.:

AF XY:

0.00319

AC XY:

2318

AN XY:

726422

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00194

Gnomad4 FIN exome

AF:

0.000385

Gnomad4 NFE exome

AF:

0.00387

Gnomad4 OTH exome

AF:

0.00239

GnomAD4 genome

AF:

0.00204

AC:

311

AN:

152320

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00347

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00266

Hom.:

Bravo

AF:

0.00210

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00200

AC:

243

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00387

EpiControl

AF:

0.00314

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Mar 02, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TUBGCP6: BP4, BP7, BS2 -

Clinical Genetics, Academic Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jul 16, 2018

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Microcephaly and chorioretinopathy 1

Benign:1

Jun 28, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.016

DANN

Benign

0.90

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0099

MetaSVM

Benign

-0.75

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.27

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.022

MVP

0.072

ClinPred

0.027

GERP RS

-7.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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