18-12308274-G-T

Position:

• chr18-12308274-G-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.-19G>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 0.107 in 1,432,188 control chromosomes in the GnomAD database, including 8,785 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (928 hom., cov: 33)
  • Exomes 𝑓: 0.11 (7857 hom.)
• Consequence: TUBB6 NM_032525.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00900

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 18-12308274-G-T is Benign according to our data. Variant chr18-12308274-G-T is described in ClinVar as [Benign]. Clinvar id is 1684207.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB6	NM_032525.3	c.-19G>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.-19G>T		5_prime_UTR_variant	1/4	1	NM_032525.3	P1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16479 AN: 150672 Hom.: 929 Cov.: 33

Gnomad AFR AF: 0.0821

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0831

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.130

GnomAD3 exomes AF: 0.119 AC: 15108 AN: 127258 Hom.: 942 AF XY: 0.118 AC XY: 8557 AN XY: 72418

Gnomad AFR exome AF: 0.0773

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.141

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.0836

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.107 AC: 137306 AN: 1281408 Hom.: 7857 Cov.: 32 AF XY: 0.109 AC XY: 68903 AN XY: 634702

Gnomad4 AFR exome AF: 0.0772

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.0908

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.109 AC: 16478 AN: 150780 Hom.: 928 Cov.: 33 AF XY: 0.110 AC XY: 8070 AN XY: 73648

Gnomad4 AFR AF: 0.0820

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0831

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0455 Hom.: 39

Bravo AF: 0.113

Asia WGS AF: 0.130 AC: 424 AN: 3244

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs11548177; hg19: chr18-12308273;