rs8086821

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr18-12308246-C-G
• chr18-12308246-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032525.3(TUBB6):​c.-47C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUBB6 NM_032525.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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>G		5_prime_UTR	Exon 1 of 4	NP_115914.1	Q9BUF5
	TUBB6	NM_001303526.2		c.-47C>G		5_prime_UTR	Exon 1 of 3	NP_001290455.1
	TUBB6	NM_001303528.2		c.-358C>G		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>G		5_prime_UTR	Exon 1 of 4	ENSP00000318697.4	Q9BUF5
	TUBB6	ENST00000591909.5	TSL:1	c.-47C>G		5_prime_UTR	Exon 1 of 4	ENSP00000465040.1	K7EJ64
	TUBB6	ENST00000586810.5	TSL:1	n.-47C>G		non_coding_transcript_exon	Exon 1 of 5	ENSP00000467348.1	K7EPE5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 22

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4740

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.0
DANN	Benign	0.45
PhyloP100		-0.15
PromoterAI		0.12	Neutral

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: rs8086821; hg19: chr18-12308245;