NM_006088.6:c.27C>G

Variant names:

• chr9-137241387-C-G
• rs1444026076
• NM_006088.6:c.27C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_006088.6(TUBB4B):​c.27C>G​(p.Ala9Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A9A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TUBB4B NM_006088.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 0 publications found

Genes affected

TUBB4B (HGNC:20771): (tubulin beta 4B class IVb) Enables double-stranded RNA binding activity. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in microtubule. Implicated in Leber congenital amaurosis with early-onset deafness. [provided by Alliance of Genome Resources, Apr 2022]

TUBB4B Gene-Disease associations (from GenCC):

• TUBB4B-related ciliopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Leber congenital amaurosis with early-onset deafness

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• BP7: Synonymous conserved (PhyloP=-0.113 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006088.6. 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
	TUBB4B	NM_006088.6	MANE Select	c.27C>G	p.Ala9Ala	synonymous	Exon 1 of 4	NP_006079.1	P68371

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB4B	ENST00000340384.5	TSL:1 MANE Select	c.27C>G	p.Ala9Ala	synonymous	Exon 1 of 4	ENSP00000341289.4	P68371
	TUBB4B	ENST00000604929.1	TSL:1	n.100C>G		non_coding_transcript_exon	Exon 1 of 3
	TUBB4B	ENST00000938213.1		c.27C>G	p.Ala9Ala	synonymous	Exon 1 of 4	ENSP00000608272.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448700 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 721076

African (AFR) AF: 0.00 AC: 0 AN: 32198

American (AMR) AF: 0.00 AC: 0 AN: 44296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

East Asian (EAS) AF: 0.00 AC: 0 AN: 38158

South Asian (SAS) AF: 0.00 AC: 0 AN: 85770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108058

Other (OTH) AF: 0.00 AC: 0 AN: 59960

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		-0.11
PromoterAI		-0.17	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: rs1444026076; hg19: chr9-140135839;