18-12308378-C-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.57+29C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,367,594 control chromosomes in the GnomAD database, including 405,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.67 (35851 hom., cov: 32)
  • Exomes 𝑓: 0.78 (369338 hom.)
• Consequence: TUBB6 NM_032525.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0950

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=-0.7).
• BP6: Variant 18-12308378-C-A is Benign according to our data. Variant chr18-12308378-C-A is described in ClinVar as [Benign]. Clinvar id is 1684208.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB6	NM_032525.3	c.57+29C>A		intron_variant		ENST00000317702.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB6	ENST00000317702.10	c.57+29C>A		intron_variant		1	NM_032525.3	P1

Frequencies

GnomAD3 genomes AF: 0.675 AC: 101802 AN: 150914 Hom.: 35839 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.675

GnomAD3 exomes AF: 0.763 AC: 79109 AN: 103704 Hom.: 30190 AF XY: 0.770 AC XY: 46659 AN XY: 60604

Gnomad AFR exome AF: 0.501

Gnomad AMR exome AF: 0.629

Gnomad ASJ exome AF: 0.754

Gnomad EAS exome AF: 0.644

Gnomad SAS exome AF: 0.791

Gnomad FIN exome AF: 0.826

Gnomad NFE exome AF: 0.801

Gnomad OTH exome AF: 0.758

GnomAD4 exome AF: 0.776 AC: 944557 AN: 1216574 Hom.: 369338 Cov.: 27 AF XY: 0.777 AC XY: 464684 AN XY: 598014

Gnomad4 AFR exome AF: 0.466

Gnomad4 AMR exome AF: 0.614

Gnomad4 ASJ exome AF: 0.756

Gnomad4 EAS exome AF: 0.598

Gnomad4 SAS exome AF: 0.792

Gnomad4 FIN exome AF: 0.815

Gnomad4 NFE exome AF: 0.791

Gnomad4 OTH exome AF: 0.751

GnomAD4 genome AF: 0.674 AC: 101831 AN: 151020 Hom.: 35851 Cov.: 32 AF XY: 0.676 AC XY: 49898 AN XY: 73796

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.677

Alfa AF: 0.712 Hom.: 5734

Bravo AF: 0.650

Asia WGS AF: 0.661 AC: 2107 AN: 3192

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	-0.70
Cadd	Benign	7.4
Dann	Benign	0.72

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: rs8086993; hg19: chr18-12308377;