18-12325143-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_032525.3(TUBB6):c.354C>T(p.Asp118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,611,960 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0096 (14 hom., cov: 32)
  • Exomes 𝑓: 0.012 (139 hom.)
• Consequence: TUBB6 NM_032525.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.89

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 18-12325143-C-T is Benign according to our data. Variant chr18-12325143-C-T is described in ClinVar as [Benign]. Clinvar id is 2648593.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.89 with no splicing effect.
• BS2: High AC in GnomAd at 1455 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB6	NM_032525.3	c.354C>T	p.Asp118=	synonymous_variant	4/4	ENST00000317702.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB6	ENST00000317702.10	c.354C>T	p.Asp118=	synonymous_variant	4/4	1	NM_032525.3	P1

Frequencies

GnomAD3 genomes AF: 0.00956 AC: 1455 AN: 152188 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00246

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00523

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0366

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.00983 AC: 2454 AN: 249750 Hom.: 19 AF XY: 0.00996 AC XY: 1344 AN XY: 134906

Gnomad AFR exome AF: 0.00203

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.00536

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00122

Gnomad FIN exome AF: 0.0333

Gnomad NFE exome AF: 0.0126

Gnomad OTH exome AF: 0.0115

GnomAD4 exome AF: 0.0116 AC: 16939 AN: 1459654 Hom.: 139 Cov.: 31 AF XY: 0.0114 AC XY: 8251 AN XY: 725888

Gnomad4 AFR exome AF: 0.00143

Gnomad4 AMR exome AF: 0.00372

Gnomad4 ASJ exome AF: 0.00659

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00145

Gnomad4 FIN exome AF: 0.0313

Gnomad4 NFE exome AF: 0.0127

Gnomad4 OTH exome AF: 0.0100

GnomAD4 genome AF: 0.00955 AC: 1455 AN: 152306 Hom.: 14 Cov.: 32 AF XY: 0.0104 AC XY: 773 AN XY: 74474

Gnomad4 AFR AF: 0.00245

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0366

Gnomad4 NFE AF: 0.0120

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.0101 Hom.: 3

Bravo AF: 0.00702

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0108

EpiControl AF: 0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

TUBB6: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	3.6
Dann	Benign	0.92

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

LitVar

Other links and lift over

dbSNP: rs61743679; hg19: chr18-12325142;