rs368378157

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020461.4(TUBGCP6):c.1304G>A(p.Gly435Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000641 in 1,560,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

TUBGCP6
NM_020461.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 4.92

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: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
TUBGCP6	NM_020461.4 link	c.1304G>A	p.Gly435Asp	missense_variant	Exon 5 of 25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3 link	n.1868G>A		non_coding_transcript_exon_variant	Exon 5 of 20
TUBGCP6	XR_007067982.1 link	n.1868G>A		non_coding_transcript_exon_variant	Exon 5 of 19
TUBGCP6	XR_938347.3 link	n.1868G>A		non_coding_transcript_exon_variant	Exon 5 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
TUBGCP6	ENST00000248846.10 link	c.1304G>A	p.Gly435Asp	missense_variant	Exon 5 of 25	1	NM_020461.4	ENSP00000248846.5
TUBGCP6	ENST00000439308.7 link	n.1304G>A		non_coding_transcript_exon_variant	Exon 5 of 25	1		ENSP00000397387.2
TUBGCP6	ENST00000498611.5 link	n.1837G>A		non_coding_transcript_exon_variant	Exon 5 of 23	1
TUBGCP6	ENST00000434349.1 link	c.533G>A	p.Gly178Asp	missense_variant	Exon 4 of 6	5		ENSP00000409650.1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000580

AC:

AN:

172368

AF XY:

0.0000110

show subpopulations

Gnomad AFR exome

AF:

0.0000897

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000355

AC:

AN:

1407942

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

694726

show subpopulations

African (AFR)

AF:

0.0000914

AC:

AN:

32838

American (AMR)

AF:

0.00

AC:

AN:

35558

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24586

East Asian (EAS)

AF:

0.00

AC:

AN:

38136

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50008

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5136

European-Non Finnish (NFE)

AF:

9.22e-7

AC:

AN:

1084158

Other (OTH)

AF:

0.00

AC:

AN:

58380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.0000332

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000171

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 11, 2014

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inborn genetic diseases

Uncertain:1

Mar 01, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1304G>A (p.G435D) alteration is located in exon 5 (coding exon 5) of the TUBGCP6 gene. This alteration results from a G to A substitution at nucleotide position 1304, causing the glycine (G) at amino acid position 435 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

not provided

Uncertain:1

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 435 of the TUBGCP6 protein (p.Gly435Asp). This variant is present in population databases (rs368378157, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TUBGCP6-related conditions. ClinVar contains an entry for this variant (Variation ID: 212505). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.64

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.025

MetaRNN

Pathogenic

0.84

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;.

PhyloP100

4.9

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-4.9

D;D

Sift

Uncertain

0.013

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.87

ClinPred

0.94

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.42

gMVP

0.85

Mutation Taster

=48/52

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over