6-112071450-G-T

Position:

• chr6-112071450-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000368662.10(TUBE1):​c.1390C>A​(p.Pro464Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUBE1 ENST00000368662.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1923852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBE1	NM_016262.5	c.1390C>A	p.Pro464Thr	missense_variant	12/12	ENST00000368662.10	NP_057346.1
TUBE1	XM_047418854.1	c.1258C>A	p.Pro420Thr	missense_variant	11/11		XP_047274810.1
TUBE1	XM_047418855.1	c.1165C>A	p.Pro389Thr	missense_variant	10/10		XP_047274811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBE1	ENST00000368662.10	c.1390C>A	p.Pro464Thr	missense_variant	12/12	1	NM_016262.5	ENSP00000357651.5
TUBE1	ENST00000604814.5	n.1599C>A		non_coding_transcript_exon_variant	10/10	5
TUBE1	ENST00000605457.5	n.*786C>A		non_coding_transcript_exon_variant	12/12	5		ENSP00000474458.1
TUBE1	ENST00000605457.5	n.*786C>A		3_prime_UTR_variant	12/12	5		ENSP00000474458.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.1390C>A (p.P464T) alteration is located in exon 12 (coding exon 12) of the TUBE1 gene. This alteration results from a C to A substitution at nucleotide position 1390, causing the proline (P) at amino acid position 464 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Benign	0.50
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.97	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.010	N
REVEL	Uncertain	0.36
Sift	Benign	0.098	T
Sift4G	Benign	0.48	T
Polyphen		0.0090	B
Vest4		0.24
MutPred		0.25		Loss of catalytic residue at N462 (P = 0.1004);
MVP		0.69
MPC		0.067
ClinPred		0.60	D
GERP RS		5.6
Varity_R		0.058
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-112392653;