rs147989796

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020461.4(TUBGCP6):c.2574G>C(p.Trp858Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000783 in 1,511,834 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00083 ( 3 hom., cov: 34)

Exomes 𝑓: 0.00078 ( 25 hom. )

Consequence

TUBGCP6
NM_020461.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.92

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

microcephaly and chorioretinopathy 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, ClinGen

TUBGCP6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003079027).

BP6

Variant 22-50221785-C-G is Benign according to our data. Variant chr22-50221785-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 212510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000827 (126/152306) while in subpopulation AMR AF = 0.0081 (124/15302). AF 95% confidence interval is 0.00694. There are 3 homozygotes in GnomAd4. There are 66 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
TUBGCP6	NM_020461.4 link	c.2574G>C	p.Trp858Cys	missense_variant	Exon 16 of 25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3 link	n.3138G>C		non_coding_transcript_exon_variant	Exon 16 of 20
TUBGCP6	XR_938347.3 link	n.3138G>C		non_coding_transcript_exon_variant	Exon 16 of 23
TUBGCP6	XR_007067982.1 link	n.3048+243G>C		intron_variant	Intron 15 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10 link	c.2574G>C	p.Trp858Cys	missense_variant	Exon 16 of 25	1	NM_020461.4	ENSP00000248846.5

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00811

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.00548

AC:

959

AN:

174938

AF XY:

0.00387

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0452

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000237

Gnomad OTH exome

AF:

0.00397

GnomAD4 exome

AF:

0.000778

AC:

1058

AN:

1359528

Hom.:

Cov.:

AF XY:

0.000608

AC XY:

404

AN XY:

664700

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30160

American (AMR)

AF:

0.0361

AC:

1044

AN:

28906

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19820

East Asian (EAS)

AF:

0.00

AC:

AN:

38690

South Asian (SAS)

AF:

0.00

AC:

AN:

69704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5276

European-Non Finnish (NFE)

AF:

0.00000565

AC:

AN:

1062060

Other (OTH)

AF:

0.000143

AC:

AN:

55902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

122

184

245

306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000827

AC:

126

AN:

152306

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41578

American (AMR)

AF:

0.00810

AC:

124

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68004

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00175

Hom.:

Bravo

AF:

0.00274

ExAC

AF:

0.00574

AC:

674

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jun 25, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Apr 22, 2015

Genetic Services Laboratory, University of Chicago

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

-0.70

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.0040

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.0094

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

PhyloP100

-3.9

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.0050

Sift

Benign

0.19

T;T

Sift4G

Benign

0.21

T;T

Vest4

0.10

ClinPred

0.020

GERP RS

-7.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.066

gMVP

0.35

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over