dbSNP rs758201280: TUBGCP6:p.Thr830Met (chr22-50221870-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020461.4(TUBGCP6):c.2489C>T(p.Thr830Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,513,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T830T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TUBGCP6
NM_020461.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.261

Publications

4 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), ClinGen, G2P, Orphanet

TUBGCP6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0100236535).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020461.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP6	NM_020461.4	MANE Select	c.2489C>T	p.Thr830Met	missense	Exon 16 of 25	NP_065194.3	Q96RT7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TUBGCP6	ENST00000248846.10	TSL:1 MANE Select	c.2489C>T	p.Thr830Met	missense	Exon 16 of 25	ENSP00000248846.5	Q96RT7-1
TUBGCP6	ENST00000439308.7	TSL:1	n.2489C>T		non_coding_transcript_exon	Exon 16 of 25	ENSP00000397387.2	E7EQL8
TUBGCP6	ENST00000489511.5	TSL:1	n.502C>T		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.0164

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000226

AC:

AN:

177022

AF XY:

0.0000319

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000125

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000234

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000112

AC:

153

AN:

1361672

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

666622

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30364

American (AMR)

AF:

0.00

AC:

AN:

30548

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20032

East Asian (EAS)

AF:

0.0000258

AC:

AN:

38732

South Asian (SAS)

AF:

0.0000139

AC:

AN:

71826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5290

European-Non Finnish (NFE)

AF:

0.000135

AC:

144

AN:

1063436

Other (OTH)

AF:

0.000125

AC:

AN:

56072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.000131

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.000102

Hom.:

Bravo

AF:

0.000181

ExAC

AF:

0.0000337

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.8

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.020

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.38

M_CAP

Benign

0.032

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

PhyloP100

0.26

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.2

REVEL

Benign

0.084

Sift

Benign

0.10

Sift4G

Uncertain

0.040

Polyphen

0.93

Vest4

0.092

MVP

0.23

MPC

0.17

ClinPred

0.061

GERP RS

-5.0

Varity_R

0.014

gMVP

0.26

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over