18-12311026-C-T

Variant names:

• chr18-12311026-C-T
• NM_032525.3:c.250C>T

Variant summary

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

The NM_032525.3(TUBB6):​c.250C>T​(p.Leu84Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUBB6 NM_032525.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.200

Genes affected

TUBB6 (HGNC:20776): (tubulin beta 6 class V) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBB6	NM_032525.3	c.250C>T	p.Leu84Phe	missense_variant	Exon 3 of 4	ENST00000317702.10	NP_115914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBB6	ENST00000317702.10	c.250C>T	p.Leu84Phe	missense_variant	Exon 3 of 4	1	NM_032525.3	ENSP00000318697.4

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

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.250C>T (p.L84F) alteration is located in exon 3 (coding exon 3) of the TUBB6 gene. This alteration results from a C to T substitution at nucleotide position 250, causing the leucine (L) at amino acid position 84 to be replaced by a phenylalanine (F). 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	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;T;T;T;T;.;T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.053	N
LIST_S2	Uncertain	0.93	D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.51	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.078	D
MutationAssessor	Pathogenic	3.1	.;M;.;.;.;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.0	.;N;.;.;.;.;.;.
REVEL	Uncertain	0.48
Sift	Uncertain	0.0020	.;D;.;.;.;.;.;.
Sift4G	Uncertain	0.021	D;T;D;D;D;D;D;D
Polyphen		0.94	.;P;.;.;.;.;.;.
Vest4		0.36, 0.52, 0.38, 0.52, 0.53, 0.32
MutPred		0.36		Gain of disorder (P = 0.2129);Gain of disorder (P = 0.2129);Gain of disorder (P = 0.2129);Gain of disorder (P = 0.2129);Gain of disorder (P = 0.2129);Gain of disorder (P = 0.2129);Gain of disorder (P = 0.2129);.;
MVP		0.90
MPC		2.0
ClinPred		0.97	D
GERP RS		3.9
Varity_R		0.32
gMVP		0.87

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: chr18-12311025;