rs864321677
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP5
The NM_178014.4(TUBB):c.665A>T(p.Tyr222Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. Y222Y) has been classified as Benign.
Frequency
Genomes: not found (cov: 32)
Consequence
TUBB
NM_178014.4 missense
NM_178014.4 missense
Scores
1
8
8
Clinical Significance
Conservation
PhyloP100: 9.01
Genes affected
TUBB (HGNC:20778): (tubulin beta class I) This gene encodes a beta tubulin protein. This protein forms a dimer with alpha tubulin and acts as a structural component of microtubules. Mutations in this gene cause cortical dysplasia, complex, with other brain malformations 6. Alternative splicing results in multiple splice variants. There are multiple pseudogenes for this gene on chromosomes 1, 6, 7, 8, 9, and 13. [provided by RefSeq, Jun 2014]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TUBB. . Gene score misZ 5.6252 (greater than the threshold 3.09). Trascript score misZ 8.3435 (greater than threshold 3.09). GenCC has associacion of gene with multiple benign circumferential skin creases on limbs 1, complex cortical dysplasia with other brain malformations 6, multiple benign circumferential skin creases on limbs, TUBB3-related tubulinopathy.
PP5
Variant 6-30723727-A-T is Pathogenic according to our data. Variant chr6-30723727-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 218926.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-30723727-A-T is described in UniProt as null. Variant chr6-30723727-A-T is described in UniProt as null. Variant chr6-30723727-A-T is described in UniProt as null. Variant chr6-30723727-A-T is described in UniProt as null. Variant chr6-30723727-A-T is described in UniProt as null. Variant chr6-30723727-A-T is described in UniProt as null. Variant chr6-30723727-A-T is described in UniProt as null. Variant chr6-30723727-A-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBB | NM_178014.4 | c.665A>T | p.Tyr222Phe | missense_variant | 4/4 | ENST00000327892.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBB | ENST00000327892.13 | c.665A>T | p.Tyr222Phe | missense_variant | 4/4 | 1 | NM_178014.4 | P1 | |
ENST00000607476.1 | n.151T>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Multiple benign circumferential skin creases on limbs 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 11, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift4G
Benign
T;T;T;T
Polyphen
P;.;.;.
Vest4
MutPred
Loss of catalytic residue at L217 (P = 0.1155);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at