17-35148982-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001267052.2(UNC45B):c.178G>A(p.Val60Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 1,613,820 control chromosomes in the GnomAD database, including 3,166 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.050 ( 334 hom., cov: 32)

Exomes 𝑓: 0.048 ( 2832 hom. )

Consequence

UNC45B
NM_001267052.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.91

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013712049).

BP6

Variant 17-35148982-G-A is Benign according to our data. Variant chr17-35148982-G-A is described in ClinVar as [Benign]. Clinvar id is 1248888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC45B	NM_001267052.2 link	c.178G>A	p.Val60Ile	missense_variant	Exon 3 of 20	ENST00000394570.7	NP_001253981.1	Q8IWX7-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UNC45B	ENST00000394570.7 link	c.178G>A	p.Val60Ile	missense_variant	Exon 3 of 20	1	NM_001267052.2	ENSP00000378071.2	Q8IWX7-3
UNC45B	ENST00000591048.2 link	c.178G>A	p.Val60Ile	missense_variant	Exon 2 of 17	1		ENSP00000468335.1	Q8IWX7-2
UNC45B	ENST00000268876.9 link	c.178G>A	p.Val60Ile	missense_variant	Exon 3 of 20	5		ENSP00000268876.4	Q8IWX7-1

Frequencies

GnomAD3 genomes

AF:

0.0500

AC:

7598

AN:

152018

Hom.:

333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.0714

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.0635

Gnomad SAS

AF:

0.0912

Gnomad FIN

AF:

0.0979

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0439

Gnomad OTH

AF:

0.0421

GnomAD3 exomes

AF:

0.0745

AC:

18720

AN:

251342

Hom.:

1352

AF XY:

0.0699

AC XY:

9489

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00997

Gnomad AMR exome

AF:

0.216

Gnomad ASJ exome

AF:

0.0163

Gnomad EAS exome

AF:

0.0691

Gnomad SAS exome

AF:

0.0870

Gnomad FIN exome

AF:

0.0926

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0603

GnomAD4 exome

AF:

0.0479

AC:

69981

AN:

1461684

Hom.:

2832

Cov.:

AF XY:

0.0485

AC XY:

35234

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.00756

Gnomad4 AMR exome

AF:

0.205

Gnomad4 ASJ exome

AF:

0.0155

Gnomad4 EAS exome

AF:

0.0617

Gnomad4 SAS exome

AF:

0.0855

Gnomad4 FIN exome

AF:

0.0908

Gnomad4 NFE exome

AF:

0.0384

Gnomad4 OTH exome

AF:

0.0451

GnomAD4 genome

AF:

0.0500

AC:

7611

AN:

152136

Hom.:

334

Cov.:

AF XY:

0.0553

AC XY:

4115

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0116

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.0634

Gnomad4 SAS

AF:

0.0909

Gnomad4 FIN

AF:

0.0979

Gnomad4 NFE

AF:

0.0440

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0445

Hom.:

522

Bravo

AF:

0.0505

TwinsUK

AF:

0.0372

AC:

138

ALSPAC

AF:

0.0345

AC:

133

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.0381

AC:

328

ExAC

AF:

0.0670

AC:

8132

Asia WGS

AF:

0.0760

AC:

264

AN:

3478

EpiCase

AF:

0.0360

EpiControl

AF:

0.0341

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.050

T;.;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.73

T;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.62

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.62

N;N;.

REVEL

Benign

0.063

Sift

Benign

0.13

T;T;.

Sift4G

Benign

0.23

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.053

MPC

0.079

ClinPred

0.0036

GERP RS

1.5

Varity_R

0.050

gMVP

0.072

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over