Genetic Variant TUBGCP6:p.Gly1189Arg (chr22-50220794-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_020461.4(TUBGCP6):c.3565G>C(p.Gly1189Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TUBGCP6
NM_020461.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.82

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34546256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP6	NM_020461.4 link	c.3565G>C	p.Gly1189Arg	missense_variant	Exon 16 of 25	ENST00000248846.10	NP_065194.3	Q96RT7-1
TUBGCP6	XR_001755343.3 link	n.4129G>C		non_coding_transcript_exon_variant	Exon 16 of 20
TUBGCP6	XR_938347.3 link	n.4129G>C		non_coding_transcript_exon_variant	Exon 16 of 23
TUBGCP6	XR_007067982.1 link	n.3049-779G>C		intron_variant	Intron 15 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TUBGCP6	ENST00000248846.10 link	c.3565G>C	p.Gly1189Arg	missense_variant	Exon 16 of 25	1	NM_020461.4	ENSP00000248846.5	Q96RT7-1
TUBGCP6	ENST00000439308.7 link	n.3565G>C		non_coding_transcript_exon_variant	Exon 16 of 25	1		ENSP00000397387.2	E7EQL8
TUBGCP6	ENST00000498611.5 link	n.3617+481G>C		intron_variant	Intron 16 of 22	1
TUBGCP6	ENST00000491449.5 link	n.1872G>C		non_coding_transcript_exon_variant	Exon 8 of 16	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450402

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721570

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32866

American (AMR)

AF:

0.00

AC:

AN:

41720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25856

East Asian (EAS)

AF:

0.0000259

AC:

AN:

38570

South Asian (SAS)

AF:

0.00

AC:

AN:

84926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107826

Other (OTH)

AF:

0.00

AC:

AN:

59804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.0072

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.5

M;.

PhyloP100

2.8

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.80

P;.

Vest4

0.27

MutPred

0.59

Gain of MoRF binding (P = 0.0086);Gain of MoRF binding (P = 0.0086);

MVP

0.71

MPC

0.58

ClinPred

0.91

GERP RS

3.1

PromoterAI

-0.0032

Neutral

(source)

Varity_R

0.13

gMVP

0.62

Mutation Taster

=78/22

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over