rs4838865

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020461.4(TUBGCP6):c.1700T>C(p.Leu567Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 1,613,956 control chromosomes in the GnomAD database, including 482,265 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 51135 hom., cov: 32)

Exomes 𝑓: 0.77 ( 431130 hom. )

Consequence

TUBGCP6
NM_020461.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.798

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=6.319099E-7).

BP6

Variant 22-50226183-A-G is Benign according to our data. Variant chr22-50226183-A-G is described in ClinVar as [Benign]. Clinvar id is 518329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50226183-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP6	NM_020461.4 link	c.1700T>C	p.Leu567Ser	missense_variant	Exon 9 of 25	ENST00000248846.10	NP_065194.3	Q96RT7-1
TUBGCP6	XR_001755343.3 link	n.2264T>C		non_coding_transcript_exon_variant	Exon 9 of 20
TUBGCP6	XR_007067982.1 link	n.2264T>C		non_coding_transcript_exon_variant	Exon 9 of 19
TUBGCP6	XR_938347.3 link	n.2264T>C		non_coding_transcript_exon_variant	Exon 9 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10 link	c.1700T>C	p.Leu567Ser	missense_variant	Exon 9 of 25	1	NM_020461.4	ENSP00000248846.5		Q96RT7-1

Frequencies

GnomAD3 genomes

AF:

0.814

AC:

123790

AN:

152028

Hom.:

51086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.952

Gnomad AMI

AF:

0.686

Gnomad AMR

AF:

0.720

Gnomad ASJ

AF:

0.713

Gnomad EAS

AF:

0.826

Gnomad SAS

AF:

0.894

Gnomad FIN

AF:

0.796

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.756

Gnomad OTH

AF:

0.791

GnomAD3 exomes

AF:

0.782

AC:

196476

AN:

251388

Hom.:

77655

AF XY:

0.788

AC XY:

107016

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.959

Gnomad AMR exome

AF:

0.654

Gnomad ASJ exome

AF:

0.719

Gnomad EAS exome

AF:

0.830

Gnomad SAS exome

AF:

0.890

Gnomad FIN exome

AF:

0.795

Gnomad NFE exome

AF:

0.762

Gnomad OTH exome

AF:

0.770

GnomAD4 exome

AF:

0.766

AC:

1120144

AN:

1461810

Hom.:

431130

Cov.:

AF XY:

0.769

AC XY:

559426

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.959

Gnomad4 AMR exome

AF:

0.662

Gnomad4 ASJ exome

AF:

0.716

Gnomad4 EAS exome

AF:

0.828

Gnomad4 SAS exome

AF:

0.887

Gnomad4 FIN exome

AF:

0.797

Gnomad4 NFE exome

AF:

0.752

Gnomad4 OTH exome

AF:

0.779

GnomAD4 genome

AF:

0.814

AC:

123888

AN:

152146

Hom.:

51135

Cov.:

AF XY:

0.817

AC XY:

60786

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.952

Gnomad4 AMR

AF:

0.719

Gnomad4 ASJ

AF:

0.713

Gnomad4 EAS

AF:

0.826

Gnomad4 SAS

AF:

0.895

Gnomad4 FIN

AF:

0.796

Gnomad4 NFE

AF:

0.756

Gnomad4 OTH

AF:

0.786

Alfa

AF:

0.768

Hom.:

108928

Bravo

AF:

0.811

TwinsUK

AF:

0.746

AC:

2766

ALSPAC

AF:

0.743

AC:

2865

ESP6500AA

AF:

0.949

AC:

4183

ESP6500EA

AF:

0.760

AC:

6539

ExAC

AF:

0.791

AC:

96041

Asia WGS

AF:

0.847

AC:

2945

AN:

3478

EpiCase

AF:

0.761

EpiControl

AF:

0.756

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Microcephaly and chorioretinopathy 1

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:1

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.84

DANN

Benign

0.32

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.023

T;T

MetaRNN

Benign

6.3e-7

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.51

N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.040

Sift

Benign

0.69

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0050

B;.

Vest4

0.063

MPC

0.15

ClinPred

0.0014

GERP RS

-5.7

Varity_R

0.013

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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