rs115847686
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_018943.3(TUBA8):c.250C>T(p.Arg84Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,614,136 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0053 ( 7 hom., cov: 32)
Exomes 𝑓: 0.00055 ( 7 hom. )
Consequence
TUBA8
NM_018943.3 missense
NM_018943.3 missense
Scores
3
11
4
Clinical Significance
Conservation
PhyloP100: 2.09
Genes affected
TUBA8 (HGNC:12410): (tubulin alpha 8) This gene encodes a member of the alpha tubulin protein family. Alpha tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. Mutations in this gene are associated with polymicrogyria and optic nerve hypoplasia. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.010679781).
BP6
Variant 22-18124179-C-T is Benign according to our data. Variant chr22-18124179-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 160171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0053 (807/152260) while in subpopulation AFR AF= 0.0186 (771/41542). AF 95% confidence interval is 0.0175. There are 7 homozygotes in gnomad4. There are 356 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 7 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TUBA8 | NM_018943.3 | c.250C>T | p.Arg84Cys | missense_variant | 3/5 | ENST00000330423.8 | NP_061816.1 | |
TUBA8 | NM_001193414.2 | c.52C>T | p.Arg18Cys | missense_variant | 3/5 | NP_001180343.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TUBA8 | ENST00000330423.8 | c.250C>T | p.Arg84Cys | missense_variant | 3/5 | 1 | NM_018943.3 | ENSP00000333326.3 | ||
ENSG00000288683 | ENST00000474897.6 | n.*140C>T | non_coding_transcript_exon_variant | 7/9 | 5 | ENSP00000434235.2 | ||||
ENSG00000288683 | ENST00000474897.6 | n.*140C>T | 3_prime_UTR_variant | 7/9 | 5 | ENSP00000434235.2 |
Frequencies
GnomAD3 genomes AF: 0.00528 AC: 804AN: 152142Hom.: 7 Cov.: 32
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GnomAD3 exomes AF: 0.00137 AC: 345AN: 251446Hom.: 1 AF XY: 0.000986 AC XY: 134AN XY: 135902
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GnomAD4 exome AF: 0.000553 AC: 809AN: 1461876Hom.: 7 Cov.: 30 AF XY: 0.000470 AC XY: 342AN XY: 727240
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GnomAD4 genome AF: 0.00530 AC: 807AN: 152260Hom.: 7 Cov.: 32 AF XY: 0.00478 AC XY: 356AN XY: 74446
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Dec 23, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 19, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 20, 2017 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 13, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;.;D;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
.;.;M;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
.;.;D;D
Sift4G
Uncertain
D;T;T;T
Polyphen
0.98, 0.10
.;.;D;B
Vest4
0.60, 0.62
MVP
MPC
0.83
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at