18-12308244-T-A

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.-49T>A 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 1,335,354 control chromosomes in the GnomAD database, including 395,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.67 (35120 hom., cov: 32)
  • Exomes 𝑓: 0.78 (360324 hom.)
• Consequence: TUBB6 NM_032525.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.481

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 18-12308244-T-A is Benign according to our data. Variant chr18-12308244-T-A is described in ClinVar as [Benign]. Clinvar id is 1684204.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.-49T>A		5_prime_UTR_variant	1/4	ENST00000317702.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB6	ENST00000317702.10	c.-49T>A		5_prime_UTR_variant	1/4	1	NM_032525.3	P1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 100035 AN: 148630 Hom.: 35109 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.673

GnomAD3 exomes AF: 0.749 AC: 61364 AN: 81930 Hom.: 23358 AF XY: 0.760 AC XY: 35996 AN XY: 47370

Gnomad AFR exome AF: 0.487

Gnomad AMR exome AF: 0.592

Gnomad ASJ exome AF: 0.748

Gnomad EAS exome AF: 0.652

Gnomad SAS exome AF: 0.789

Gnomad FIN exome AF: 0.821

Gnomad NFE exome AF: 0.804

Gnomad OTH exome AF: 0.740

GnomAD4 exome AF: 0.776 AC: 921169 AN: 1186616 Hom.: 360324 Cov.: 21 AF XY: 0.777 AC XY: 453593 AN XY: 583814

Gnomad4 AFR exome AF: 0.467

Gnomad4 AMR exome AF: 0.605

Gnomad4 ASJ exome AF: 0.755

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: 100064 AN: 148738 Hom.: 35120 Cov.: 32 AF XY: 0.674 AC XY: 48894 AN XY: 72508

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.772

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.675

Alfa AF: 0.653 Hom.: 2272

Bravo AF: 0.651

Asia WGS AF: 0.653 AC: 2042 AN: 3130

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	6.7
Dann	Benign	0.64

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: rs8087840; hg19: chr18-12308243; COSMIC: COSV58354432; COSMIC: COSV58354432;