rs77191445
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006086.4(TUBB3):c.277+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00698 in 1,607,286 control chromosomes in the GnomAD database, including 653 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_006086.4 splice_region, intron
Scores
Clinical Significance
Conservation
Publications
- TUBB3-related tubulinopathyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- complex cortical dysplasia with other brain malformations 1Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae), Orphanet
- fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvementInheritance: AD Classification: STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- congenital fibrosis of extraocular musclesInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- tubulinopathy-associated dysgyriaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_006086.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TUBB3 | TSL:1 MANE Select | c.277+8C>T | splice_region intron | N/A | ENSP00000320295.7 | Q13509-1 | |||
| ENSG00000198211 | TSL:2 | c.1318+8C>T | splice_region intron | N/A | ENSP00000451560.1 | A0A0B4J269 | |||
| TUBB3 | TSL:1 | n.*260+8C>T | splice_region intron | N/A | ENSP00000451985.1 | G3V4U2 |
Frequencies
GnomAD3 genomes AF: 0.0369 AC: 5614AN: 152098Hom.: 351 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00968 AC: 2433AN: 251304 AF XY: 0.00718 show subpopulations
GnomAD4 exome AF: 0.00384 AC: 5582AN: 1455070Hom.: 299 Cov.: 29 AF XY: 0.00331 AC XY: 2401AN XY: 724344 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0370 AC: 5638AN: 152216Hom.: 354 Cov.: 33 AF XY: 0.0360 AC XY: 2678AN XY: 74438 show subpopulations
Age Distribution
ClinVar
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at