NM_032525.3:c.-19G>T

Variant names:

• chr18-12308274-G-T
• rs11548177
• NM_032525.3:c.-19G>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.-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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00900
• Publications: 9 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 18-12308274-G-T is Benign according to our data. Variant chr18-12308274-G-T is described in ClinVar as Benign. ClinVar VariationId is 1684207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.152 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.-19G>T		5_prime_UTR	Exon 1 of 4	NP_115914.1	Q9BUF5
	TUBB6	NM_001303524.1		c.-19G>T		5_prime_UTR	Exon 2 of 5	NP_001290453.1	Q9BUF5
	TUBB6	NM_001303526.2		c.-19G>T		5_prime_UTR	Exon 1 of 3	NP_001290455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB6	ENST00000317702.10	TSL:1 MANE Select	c.-19G>T		5_prime_UTR	Exon 1 of 4	ENSP00000318697.4	Q9BUF5
	TUBB6	ENST00000591909.5	TSL:1	c.-19G>T		5_prime_UTR	Exon 1 of 4	ENSP00000465040.1	K7EJ64
	TUBB6	ENST00000586810.5	TSL:1	n.-19G>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000467348.1	K7EPE5

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

GnomAD2 exomes AF: 0.119 AC: 15108 AN: 127258 AF XY: 0.118

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 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

African (AFR) AF: 0.0772 AC: 2014 AN: 26104

American (AMR) AF: 0.161 AC: 4506 AN: 27914

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 3222 AN: 20760

East Asian (EAS) AF: 0.183 AC: 4833 AN: 26424

South Asian (SAS) AF: 0.115 AC: 7794 AN: 67882

European-Finnish (FIN) AF: 0.0908 AC: 3506 AN: 38624

Middle Eastern (MID) AF: 0.154 AC: 540 AN: 3514

European-Non Finnish (NFE) AF: 0.103 AC: 105144 AN: 1019576

Other (OTH) AF: 0.114 AC: 5747 AN: 50610

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

African (AFR) AF: 0.0820 AC: 3394 AN: 41368

American (AMR) AF: 0.157 AC: 2376 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 540 AN: 3444

East Asian (EAS) AF: 0.159 AC: 813 AN: 5106

South Asian (SAS) AF: 0.121 AC: 582 AN: 4826

European-Finnish (FIN) AF: 0.0831 AC: 837 AN: 10078

Middle Eastern (MID) AF: 0.188 AC: 54 AN: 288

European-Non Finnish (NFE) AF: 0.111 AC: 7494 AN: 67514

Other (OTH) AF: 0.129 AC: 270 AN: 2090

Alfa AF: 0.0475 Hom.: 42

Bravo AF: 0.113

Asia WGS AF: 0.130 AC: 424 AN: 3244

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	11
DANN	Benign	0.71
PhyloP100		-0.0090
PromoterAI		0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs11548177; hg19: chr18-12308273;