chr18-12308246-C-T

Variant names:

• chr18-12308246-C-T
• rs8086821
• NM_032525.3:c.-47C>T

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.-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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.148
• Publications: 6 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=-0.75).
• BP6: Variant 18-12308246-C-T is Benign according to our data. Variant chr18-12308246-C-T is described in ClinVar as Benign. ClinVar VariationId is 1684205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 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.-47C>T		5_prime_UTR	Exon 1 of 4	NP_115914.1	Q9BUF5
	TUBB6	NM_001303526.2		c.-47C>T		5_prime_UTR	Exon 1 of 3	NP_001290455.1
	TUBB6	NM_001303528.2		c.-358C>T		5_prime_UTR	Exon 1 of 5	NP_001290457.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB6	ENST00000317702.10	TSL:1 MANE Select	c.-47C>T		5_prime_UTR	Exon 1 of 4	ENSP00000318697.4	Q9BUF5
	TUBB6	ENST00000591909.5	TSL:1	c.-47C>T		5_prime_UTR	Exon 1 of 4	ENSP00000465040.1	K7EJ64
	TUBB6	ENST00000586810.5	TSL:1	n.-47C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000467348.1	K7EPE5

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

GnomAD2 exomes AF: 0.748 AC: 64245 AN: 85892 AF XY: 0.759

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 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

African (AFR) AF: 0.469 AC: 11296 AN: 24110

American (AMR) AF: 0.603 AC: 12852 AN: 21308

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 13894 AN: 18422

East Asian (EAS) AF: 0.607 AC: 14001 AN: 23062

South Asian (SAS) AF: 0.782 AC: 44754 AN: 57218

European-Finnish (FIN) AF: 0.814 AC: 25792 AN: 31684

Middle Eastern (MID) AF: 0.738 AC: 2404 AN: 3258

European-Non Finnish (NFE) AF: 0.792 AC: 770168 AN: 972802

Other (OTH) AF: 0.753 AC: 35011 AN: 46494

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

African (AFR) AF: 0.468 AC: 19208 AN: 41070

American (AMR) AF: 0.629 AC: 9438 AN: 15006

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2536 AN: 3412

East Asian (EAS) AF: 0.606 AC: 3065 AN: 5058

South Asian (SAS) AF: 0.771 AC: 3712 AN: 4816

European-Finnish (FIN) AF: 0.817 AC: 7840 AN: 9600

Middle Eastern (MID) AF: 0.725 AC: 206 AN: 284

European-Non Finnish (NFE) AF: 0.782 AC: 52143 AN: 66658

Other (OTH) AF: 0.675 AC: 1403 AN: 2078

Alfa AF: 0.705 Hom.: 4740

Bravo AF: 0.651

Asia WGS AF: 0.655 AC: 2042 AN: 3122

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	-0.75
CADD	Benign	7.2
DANN	Benign	0.87
PhyloP100		-0.15
PromoterAI		0.016	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8086821; hg19: chr18-12308245; COSMIC: COSV58354438; COSMIC: COSV58354438;