18-12308246-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032525.3(TUBB6):c.-47C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,347,228 control chromosomes in the GnomAD database, including 398,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.67 (35168 hom., cov: 32)
  • Exomes 𝑓: 0.78 (363825 hom.)
• Consequence: TUBB6 NM_032525.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.148

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 18-12308246-C-T is Benign according to our data. Variant chr18-12308246-C-T is described in ClinVar as [Benign]. Clinvar id is 1684205.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB6	NM_032525.3	c.-47C>T		5_prime_UTR_variant	1/4	ENST00000317702.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB6	ENST00000317702.10	c.-47C>T		5_prime_UTR_variant	1/4	1	NM_032525.3	P1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 100152 AN: 148762 Hom.: 35157 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.673

GnomAD3 exomes AF: 0.748 AC: 64245 AN: 85892 Hom.: 24393 AF XY: 0.759 AC XY: 37557 AN XY: 49506

Gnomad AFR exome AF: 0.494

Gnomad AMR exome AF: 0.591

Gnomad ASJ exome AF: 0.749

Gnomad EAS exome AF: 0.651

Gnomad SAS exome AF: 0.789

Gnomad FIN exome AF: 0.818

Gnomad NFE exome AF: 0.803

Gnomad OTH exome AF: 0.738

GnomAD4 exome AF: 0.776 AC: 930172 AN: 1198358 Hom.: 363825 Cov.: 22 AF XY: 0.777 AC XY: 458477 AN XY: 590166

Gnomad4 AFR exome AF: 0.469

Gnomad4 AMR exome AF: 0.603

Gnomad4 ASJ exome AF: 0.754

Gnomad4 EAS exome AF: 0.607

Gnomad4 SAS exome AF: 0.782

Gnomad4 FIN exome AF: 0.814

Gnomad4 NFE exome AF: 0.792

Gnomad4 OTH exome AF: 0.753

GnomAD4 genome AF: 0.673 AC: 100181 AN: 148870 Hom.: 35168 Cov.: 32 AF XY: 0.675 AC XY: 48962 AN XY: 72588

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.675

Alfa AF: 0.716 Hom.: 4660

Bravo AF: 0.651

Asia WGS AF: 0.655 AC: 2042 AN: 3122

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Facial palsy, congenital, with ptosis and velopharyngeal dysfunction Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	7.2
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8086821; hg19: chr18-12308245; COSMIC: COSV58354438; COSMIC: COSV58354438;