rs183013671

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_014444.5(TUBGCP4):c.998G>A(p.Arg333His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,497,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 24)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

TUBGCP4
NM_014444.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 9.65

Publications

4 publications found

Variant links:

Genes affected

TUBGCP4 (HGNC:16691): (tubulin gamma complex component 4) This gene encodes a component of the gamma-tubulin ring complex, which is required for microtubule nucleation. In mammalian cells, the protein localizes to centrosomes in association with gamma-tubulin. Crystal structure analysis revealed a structure composed of five helical bundles arranged around conserved hydrophobic cores. An exposed surface area located in the C-terminal domain is essential and sufficient for direct binding to gamma-tubulin. Mutations in this gene that alter microtubule organization are associated with microcephaly and chorioretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

TUBGCP4 Gene-Disease associations (from GenCC):

microcephaly and chorioretinopathy 3
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
microcephaly and chorioretinopathy 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TUBGCP4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33129925).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014444.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP4	NM_014444.5	MANE Select	c.998G>A	p.Arg333His	missense	Exon 9 of 18	NP_055259.2
	TUBGCP4	NM_001286414.3		c.998G>A	p.Arg333His	missense	Exon 9 of 18	NP_001273343.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TUBGCP4	ENST00000564079.6	TSL:1 MANE Select	c.998G>A	p.Arg333His	missense	Exon 9 of 18	ENSP00000456648.2
TUBGCP4	ENST00000260383.11	TSL:1	c.998G>A	p.Arg333His	missense	Exon 9 of 18	ENSP00000260383.7
TUBGCP4	ENST00000561691.5	TSL:1	n.752G>A		non_coding_transcript_exon	Exon 7 of 17	ENSP00000455474.1

Frequencies

GnomAD3 genomes

AF:

0.0000803

AC:

AN:

124544

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000917

Gnomad EAS

AF:

0.00117

Gnomad SAS

AF:

0.000270

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000229

AC:

AN:

240396

AF XY:

0.000199

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000252

Gnomad ASJ exome

AF:

0.00204

Gnomad EAS exome

AF:

0.000925

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000634

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.000125

AC:

172

AN:

1372464

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

683486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30916

American (AMR)

AF:

0.000295

AC:

AN:

40666

Ashkenazi Jewish (ASJ)

AF:

0.00170

AC:

AN:

23538

East Asian (EAS)

AF:

0.00156

AC:

AN:

35260

South Asian (SAS)

AF:

0.000170

AC:

AN:

82478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47644

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3792

European-Non Finnish (NFE)

AF:

0.0000408

AC:

AN:

1053026

Other (OTH)

AF:

0.000145

AC:

AN:

55144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000802

AC:

AN:

124630

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

58538

show subpopulations

African (AFR)

AF:

0.0000315

AC:

AN:

31716

American (AMR)

AF:

0.00

AC:

AN:

10918

Ashkenazi Jewish (ASJ)

AF:

0.000917

AC:

AN:

3272

East Asian (EAS)

AF:

0.00117

AC:

AN:

4280

South Asian (SAS)

AF:

0.000270

AC:

AN:

3710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

172

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62844

Other (OTH)

AF:

0.00

AC:

AN:

1600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000162

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.000182

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Microcephaly and chorioretinopathy 3 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.035

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

PhyloP100

9.7

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.90

MVP

0.63

MPC

1.5

ClinPred

0.24

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.78

gMVP

0.77

Mutation Taster

=45/55

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over