17-35150068-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2
The NM_001267052.2(UNC45B):c.226G>A(p.Asp76Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000472 in 1,608,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000045 ( 0 hom. )
Consequence
UNC45B
NM_001267052.2 missense
NM_001267052.2 missense
Scores
4
9
6
Clinical Significance
Conservation
PhyloP100: 9.80
Genes affected
UNC45B (HGNC:14304): (unc-45 myosin chaperone B) This gene encodes a co-chaperone required for folding and accumulation of type II myosins. The protein consists of three tetratricopeptide repeat motifs at the N-terminus that form a complex with heat shock protein 90, a central region of unknown function that is conserved in all Unc-45 proteins, and a C-terminal Unc-45/Cro1/She4 domain. The protein is expressed at high levels in striated muscle, where its muscle myosin chaperone activity is dependent on heat shock protein 90 acting as a co-chaperone. A missense mutation in this gene has been associated with cataract development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.31972685).
BP6
?
Variant 17-35150068-G-A is Benign according to our data. Variant chr17-35150068-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3040504.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC45B | NM_001267052.2 | c.226G>A | p.Asp76Asn | missense_variant | 4/20 | ENST00000394570.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC45B | ENST00000394570.7 | c.226G>A | p.Asp76Asn | missense_variant | 4/20 | 1 | NM_001267052.2 | P4 | |
UNC45B | ENST00000591048.2 | c.226G>A | p.Asp76Asn | missense_variant | 3/17 | 1 | |||
UNC45B | ENST00000268876.9 | c.226G>A | p.Asp76Asn | missense_variant | 4/20 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152134Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000163 AC: 40AN: 246004Hom.: 0 AF XY: 0.000195 AC XY: 26AN XY: 133028
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GnomAD4 exome AF: 0.0000453 AC: 66AN: 1456368Hom.: 0 Cov.: 30 AF XY: 0.0000580 AC XY: 42AN XY: 724342
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74442
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
UNC45B-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 17, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D;.;.
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;N;N
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.
REVEL
Uncertain
Sift
Uncertain
D;D;.
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MVP
MPC
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