chr17-35148131-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001267052.2(UNC45B):c.1-133G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00463 in 985,236 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.010 ( 31 hom., cov: 32)
Exomes 𝑓: 0.0036 ( 41 hom. )
Consequence
UNC45B
NM_001267052.2 intron
NM_001267052.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.256
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 17-35148131-G-A is Benign according to our data. Variant chr17-35148131-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1214292.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0105 (1593/152250) while in subpopulation EAS AF= 0.0387 (200/5170). AF 95% confidence interval is 0.0343. There are 31 homozygotes in gnomad4. There are 808 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1585 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC45B | NM_001267052.2 | c.1-133G>A | intron_variant | ENST00000394570.7 | |||
UNC45B | NM_001033576.2 | c.-3-130G>A | intron_variant | ||||
UNC45B | XM_017024234.2 | c.1-133G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC45B | ENST00000394570.7 | c.1-133G>A | intron_variant | 1 | NM_001267052.2 | P4 | |||
UNC45B | ENST00000268876.9 | c.-3-130G>A | intron_variant | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0104 AC: 1585AN: 152132Hom.: 30 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1585
AN:
152132
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00356 AC: 2968AN: 832986Hom.: 41 AF XY: 0.00392 AC XY: 1655AN XY: 422094
GnomAD4 exome
AF:
AC:
2968
AN:
832986
Hom.:
AF XY:
AC XY:
1655
AN XY:
422094
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0105 AC: 1593AN: 152250Hom.: 31 Cov.: 32 AF XY: 0.0109 AC XY: 808AN XY: 74442
GnomAD4 genome
?
AF:
AC:
1593
AN:
152250
Hom.:
Cov.:
32
AF XY:
AC XY:
808
AN XY:
74442
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
56
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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