chr17-35183460-C-A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001267052.2(UNC45B):​c.2407C>A​(p.Arg803Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

UNC45B
NM_001267052.2 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.51

Publications

0 publications found
Variant links:
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]
UNC45B Gene-Disease associations (from GenCC):
  • myofibrillar myopathy 11
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • cataract 43
    Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • early-onset nuclear cataract
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • early-onset posterior subcapsular cataract
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.22).
BP7
Synonymous conserved (PhyloP=1.51 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UNC45BNM_001267052.2 linkc.2407C>A p.Arg803Arg synonymous_variant Exon 19 of 20 ENST00000394570.7 NP_001253981.1 Q8IWX7-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UNC45BENST00000394570.7 linkc.2407C>A p.Arg803Arg synonymous_variant Exon 19 of 20 1 NM_001267052.2 ENSP00000378071.2 Q8IWX7-3
UNC45BENST00000591048.2 linkc.2170C>A p.Arg724Arg synonymous_variant Exon 16 of 17 1 ENSP00000468335.1 Q8IWX7-2
UNC45BENST00000268876.9 linkc.2413C>A p.Arg805Arg synonymous_variant Exon 19 of 20 5 ENSP00000268876.4 Q8IWX7-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.91e-7
AC:
1
AN:
1446386
Hom.:
0
Cov.:
30
AF XY:
0.00000139
AC XY:
1
AN XY:
719408
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
32944
American (AMR)
AF:
0.00
AC:
0
AN:
42730
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25508
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38876
South Asian (SAS)
AF:
0.00
AC:
0
AN:
83960
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53038
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5674
European-Non Finnish (NFE)
AF:
9.06e-7
AC:
1
AN:
1104084
Other (OTH)
AF:
0.00
AC:
0
AN:
59572
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.22
CADD
Benign
10
DANN
Benign
0.64
PhyloP100
1.5

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs370424081; hg19: chr17-33510479; API