6-112086583-C-A

Variant names:

• chr6-112086583-C-A
• rs974271072
• NM_016262.5:c.125G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016262.5(TUBE1):​c.125G>T​(p.Ser42Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,432 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S42T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TUBE1 NM_016262.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.66
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T	p.Ser42Ile	missense	Exon 3 of 12	NP_057346.1	Q9UJT0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBE1	ENST00000368662.10	TSL:1 MANE Select	c.125G>T	p.Ser42Ile	missense	Exon 3 of 12	ENSP00000357651.5	Q9UJT0
	TUBE1	ENST00000956039.1		c.125G>T	p.Ser42Ile	missense	Exon 3 of 11	ENSP00000626098.1
	TUBE1	ENST00000937354.1		c.125G>T	p.Ser42Ile	missense	Exon 3 of 12	ENSP00000607413.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460432 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 726584

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111006

Other (OTH) AF: 0.00 AC: 0 AN: 60332

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	0.038	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		4.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.019	D
Polyphen		0.85	P
Vest4		0.39
MutPred		0.64		Loss of relative solvent accessibility (P = 0.0676)
MVP		0.85
MPC		0.24
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.60
gMVP		0.59
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs974271072; hg19: chr6-112407786;