NM_032525.3:c.57+29C>A

Variant names:

• chr18-12308378-C-A
• rs8086993
• NM_032525.3:c.57+29C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0950
• Publications: 13 publications found

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]

TUBB6 Gene-Disease associations (from GenCC):

• facial palsy, congenital, with ptosis and velopharyngeal dysfunction

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1684208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032525.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB6	NM_032525.3	MANE Select	c.57+29C>A		intron	N/A	NP_115914.1	Q9BUF5
	TUBB6	NM_001303524.1		c.57+29C>A		intron	N/A	NP_001290453.1	Q9BUF5
	TUBB6	NM_001303526.2		c.57+29C>A		intron	N/A	NP_001290455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB6	ENST00000317702.10	TSL:1 MANE Select	c.57+29C>A		intron	N/A	ENSP00000318697.4	Q9BUF5
	TUBB6	ENST00000591909.5	TSL:1	c.57+29C>A		intron	N/A	ENSP00000465040.1	K7EJ64
	TUBB6	ENST00000586810.5	TSL:1	n.57+29C>A		intron	N/A	ENSP00000467348.1	K7EPE5

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

GnomAD2 exomes AF: 0.763 AC: 79109 AN: 103704 AF XY: 0.770

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 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

African (AFR) AF: 0.466 AC: 11371 AN: 24394

American (AMR) AF: 0.614 AC: 10743 AN: 17490

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 14052 AN: 18576

East Asian (EAS) AF: 0.598 AC: 16039 AN: 26804

South Asian (SAS) AF: 0.792 AC: 38595 AN: 48744

European-Finnish (FIN) AF: 0.815 AC: 29482 AN: 36178

Middle Eastern (MID) AF: 0.732 AC: 2430 AN: 3320

European-Non Finnish (NFE) AF: 0.791 AC: 785615 AN: 992848

Other (OTH) AF: 0.751 AC: 36230 AN: 48220

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

African (AFR) AF: 0.467 AC: 19286 AN: 41324

American (AMR) AF: 0.628 AC: 9534 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2574 AN: 3462

East Asian (EAS) AF: 0.610 AC: 3115 AN: 5104

South Asian (SAS) AF: 0.771 AC: 3723 AN: 4830

European-Finnish (FIN) AF: 0.817 AC: 8372 AN: 10244

Middle Eastern (MID) AF: 0.723 AC: 211 AN: 292

European-Non Finnish (NFE) AF: 0.783 AC: 52949 AN: 67592

Other (OTH) AF: 0.677 AC: 1418 AN: 2094

Alfa AF: 0.703 Hom.: 5813

Bravo AF: 0.650

Asia WGS AF: 0.661 AC: 2107 AN: 3192

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Facial palsy, congenital, with ptosis and velopharyngeal dysfunction (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.4
DANN	Benign	0.72
PhyloP100		-0.095
PromoterAI		-0.064	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8086993; hg19: chr18-12308377;