6-112071540-C-T

Variant names:

• chr6-112071540-C-T
• NM_016262.5:c.1300G>A

Variant summary

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

The NM_016262.5(TUBE1):​c.1300G>A​(p.Gly434Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,458,896 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TUBE1 NM_016262.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62
• 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.1300G>A	p.Gly434Arg	missense	Exon 12 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.1300G>A	p.Gly434Arg	missense	Exon 12 of 12	ENSP00000357651.5	Q9UJT0
	TUBE1	ENST00000856771.1		c.1189G>A	p.Gly397Arg	missense	Exon 10 of 10	ENSP00000526830.1
	TUBE1	ENST00000956039.1		c.1159G>A	p.Gly387Arg	missense	Exon 11 of 11	ENSP00000626098.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1458896 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4 AN XY: 725742

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26018

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 85808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5526

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110344

Other (OTH) AF: 0.00 AC: 0 AN: 60224

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Uncertain	0.022	D
MutationAssessor	Pathogenic	3.5	M
PhyloP100		4.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.0	D
REVEL	Pathogenic	0.71
Sift	Benign	0.16	T
Sift4G	Benign	0.17	T
Polyphen		0.77	P
Vest4		0.49
MutPred		0.61		Gain of helix (P = 0.0854)
MVP		0.84
MPC		0.12
ClinPred		0.87	D
GERP RS		4.7
Varity_R		0.43
gMVP		0.78
Mutation Taster		=24/76	disease causing

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

hg19: chr6-112392743;