NM_032525.3:c.326G>T

Variant names:

• chr18-12325115-G-T
• NM_032525.3:c.326G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_032525.3(TUBB6):​c.326G>T​(p.Gly109Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TUBB6 NM_032525.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.86

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.975

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBB6	NM_032525.3	c.326G>T	p.Gly109Val	missense_variant	Exon 4 of 4	ENST00000317702.10	NP_115914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBB6	ENST00000317702.10	c.326G>T	p.Gly109Val	missense_variant	Exon 4 of 4	1	NM_032525.3	ENSP00000318697.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1446932 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 717818

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;D;T;T
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.97	D;D;D;D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Pathogenic	5.3	.;H;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.2	.;D;.;.
REVEL	Pathogenic	0.90
Sift	Pathogenic	0.0	.;D;.;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.98
MutPred		0.89		Loss of disorder (P = 0.0821);Loss of disorder (P = 0.0821);.;.;
MVP		0.96
MPC		2.3
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.95
gMVP		0.97

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-12325114;