NM_020461.4:c.3307C>T

Variant names:

Variant summary

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

The NM_020461.4(TUBGCP6):c.3307C>T(p.Arg1103Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00149 in 1,612,410 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts 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. R1103Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0078 ( 15 hom., cov: 34)

Exomes 𝑓: 0.00084 ( 14 hom. )

Consequence

TUBGCP6
NM_020461.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.24

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=0.0074418485).

BP6

Variant 22-50221052-G-A is Benign according to our data. Variant chr22-50221052-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50221052-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00777 (1177/151468) while in subpopulation AFR AF= 0.0272 (1119/41122). AF 95% confidence interval is 0.0259. There are 15 homozygotes in gnomad4. There are 571 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP6	NM_020461.4 link	c.3307C>T	p.Arg1103Trp	missense_variant	Exon 16 of 25	ENST00000248846.10	NP_065194.3	Q96RT7-1
TUBGCP6	XR_001755343.3 link	n.3871C>T		non_coding_transcript_exon_variant	Exon 16 of 20
TUBGCP6	XR_938347.3 link	n.3871C>T		non_coding_transcript_exon_variant	Exon 16 of 23
TUBGCP6	XR_007067982.1 link	n.3048+976C>T		intron_variant	Intron 15 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TUBGCP6	ENST00000248846.10 link	c.3307C>T	p.Arg1103Trp	missense_variant	Exon 16 of 25	1	NM_020461.4	ENSP00000248846.5	Q96RT7-1
TUBGCP6	ENST00000439308.6 link	c.3307C>T	p.Arg1103Trp	missense_variant	Exon 16 of 25	1		ENSP00000397387.2	E7EQL8
TUBGCP6	ENST00000498611.5 link	n.3617+223C>T		intron_variant	Intron 16 of 22	1
TUBGCP6	ENST00000491449.5 link	n.1614C>T		non_coding_transcript_exon_variant	Exon 8 of 16	5

Frequencies

GnomAD3 genomes

AF:

0.00776

AC:

1175

AN:

151352

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0272

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00237

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00626

GnomAD3 exomes

AF:

0.00191

AC:

481

AN:

251452

Hom.:

AF XY:

0.00129

AC XY:

175

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0261

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000840

AC:

1227

AN:

1460942

Hom.:

Cov.:

AF XY:

0.000722

AC XY:

525

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.0286

Gnomad4 AMR exome

AF:

0.00144

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000675

Gnomad4 OTH exome

AF:

0.00184

GnomAD4 genome

AF:

0.00777

AC:

1177

AN:

151468

Hom.:

Cov.:

AF XY:

0.00771

AC XY:

571

AN XY:

74020

show subpopulations

Gnomad4 AFR

AF:

0.0272

Gnomad4 AMR

AF:

0.00236

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00619

Alfa

AF:

0.00196

Hom.:

Bravo

AF:

0.00886

ESP6500AA

AF:

0.0238

AC:

105

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00248

AC:

301

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 12, 2021

GeneDx

Significance: 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

- -

Apr 19, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

T;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.93

D;D

MetaRNN

Benign

0.0074

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.7

D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;.

Vest4

0.50

MVP

0.59

MPC

0.54

ClinPred

0.036

GERP RS

4.9

Varity_R

0.14

gMVP

0.40

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