rs11439

chr17-35188145-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001267052.2(UNC45B):c.*1586A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0923 in 152,234 control chromosomes in the GnomAD database, including 816 homozygotes. 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: 𝑓 0.092 (816 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: UNC45B NM_001267052.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.552

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC45B	NM_001267052.2	c.*1586A>C		3_prime_UTR_variant	20/20	ENST00000394570.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC45B	ENST00000394570.7	c.*1586A>C		3_prime_UTR_variant	20/20	1	NM_001267052.2	P4
UNC45B	ENST00000268876.9	c.*1586A>C		3_prime_UTR_variant	20/20	5		A1

Frequencies

GnomAD3 genomes AF: 0.0922 AC: 14018 AN: 152116 Hom.: 812 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0566

Gnomad OTH AF: 0.0918

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0923 AC: 14051 AN: 152234 Hom.: 816 Cov.: 32 AF XY: 0.0978 AC XY: 7284 AN XY: 74442

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0566

Gnomad4 OTH AF: 0.0922

Alfa AF: 0.0826 Hom.: 410

Bravo AF: 0.0968

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.4
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11439; hg19: chr17-33515164;