Genetic Variant NM_016262.5:c.125G>C (chr6-112086583-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_016262.5(TUBE1):c.125G>C(p.Ser42Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,432 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: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TUBE1
NM_016262.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66

Publications

0 publications found

Variant links:

Genes affected

TUBE1 (HGNC:20775): (tubulin epsilon 1) This gene encodes a member of the tubulin superfamily. This protein localizes to the centriolar sub-distal appendages that are associated with the older of the two centrioles after centrosome duplication. This protein plays a central role in organization of the microtubules during centriole duplication. A pseudogene of this gene is found on chromosome 5.[provided by RefSeq, Jan 2009]

TUBE1 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=0.27073106).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016262.5. 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
	TUBE1	NM_016262.5	MANE Select	c.125G>C	p.Ser42Thr	missense	Exon 3 of 12	NP_057346.1	Q9UJT0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TUBE1	ENST00000368662.10	TSL:1 MANE Select	c.125G>C	p.Ser42Thr	missense	Exon 3 of 12	ENSP00000357651.5	Q9UJT0
TUBE1	ENST00000956039.1		c.125G>C	p.Ser42Thr	missense	Exon 3 of 11	ENSP00000626098.1
TUBE1	ENST00000937354.1		c.125G>C	p.Ser42Thr	missense	Exon 3 of 12	ENSP00000607413.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

250876

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

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:

0.00000342

AC:

AN:

1460432

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726584

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33434

American (AMR)

AF:

0.0000896

AC:

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.00

AC:

AN:

86182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111006

Other (OTH)

AF:

0.0000166

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.012

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.46

MutationAssessor

Benign

1.7

PhyloP100

4.7

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.3

REVEL

Benign

0.20

Sift

Uncertain

0.019

Sift4G

Benign

0.099

Polyphen

0.25

Vest4

0.33

MutPred

0.47

Gain of relative solvent accessibility (P = 0.1571)

MVP

0.73

MPC

0.094

ClinPred

0.85

GERP RS

4.3

Varity_R

0.28

gMVP

0.35

Mutation Taster

=78/22

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over