Variant 8-66080470-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033105.6(DNAJC5B):c.427G>T(p.Glu143*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00041 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 0 hom. )

Consequence

DNAJC5B
NM_033105.6 stop_gained

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41

Variant links:

Genes affected

DNAJC5B (HGNC:24138): (DnaJ heat shock protein family (Hsp40) member C5 beta) This gene encodes a member of the DNAJ heat shock protein 40 family of co-chaperone proteins that is characterized by an N-terminal DNAJ domain, a linker region, and a cysteine-rich C-terminal domain. The encoded protein, together with heat shock protein 70, is thought to regulate the proper folding of other proteins. The orthologous mouse protein is membrane-associated and is targeted to the trans-golgi network. [provided by RefSeq, Mar 2017]

DNAJC5B links:

DNAJC5B (HGNC:):

DNAJC5B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5B	NM_033105.6 linkuse as main transcript	c.427G>T	p.Glu143*	stop_gained	5/6	ENST00000276570.10	NP_149096.2	Q9UF47A0A024R7Z1
DNAJC5B	NM_001349432.2 linkuse as main transcript	c.427G>T	p.Glu143*	stop_gained	5/6		NP_001336361.1
DNAJC5B	XM_011517620.3 linkuse as main transcript	c.427G>T	p.Glu143*	stop_gained	5/6		XP_011515922.1
DNAJC5B	NR_146171.2 linkuse as main transcript	n.2265G>T		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAJC5B	ENST00000276570.10 linkuse as main transcript	c.427G>T	p.Glu143*	stop_gained	5/6	1	NM_033105.6	ENSP00000276570.5	Q9UF47
DNAJC5B	ENST00000519330.1 linkuse as main transcript	n.2204G>T		non_coding_transcript_exon_variant	6/7	1
DNAJC5B	ENST00000524076.5 linkuse as main transcript	n.*5G>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000500

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000459

AC:

115

AN:

250602

Hom.:

AF XY:

0.000413

AC XY:

AN XY:

135470

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000530

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000401

AC:

586

AN:

1461722

Hom.:

Cov.:

AF XY:

0.000386

AC XY:

281

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000448

Gnomad4 OTH exome

AF:

0.000397

GnomAD4 genome

AF:

0.000499

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000431

Hom.:

Bravo

AF:

0.000574

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000436

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000772

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Oct 16, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.27

Vest4

0.19

GERP RS

3.5

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