Genetic Variant DNAJB5:c.-175C>T (chr9-34989789-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001349723.3(DNAJB5):c.-175C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 1,231,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

DNAJB5
NM_001349723.3 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.795

Publications

0 publications found

Variant links:

Genes affected

DNAJB5 (HGNC:14887): (DnaJ heat shock protein family (Hsp40) member B5) This gene encodes a member of the DNAJ heat shock protein 40 family of co-chaperone proteins. The encoded protein contains an N-terminal DNAJ domain and a C-terminal substrate binding domain but lacks the cysteine-rich domain found in other DNAJ family members. In mice, a multi-protein complex containing this protein, thioredoxin 1, and histone deacetylase 4, serves as a master negative regulator of cardiac hypertrophy. [provided by RefSeq, Mar 2017]

DNAJB5 links:

DNAJB5-DT (HGNC:49846): (DNAJB5 divergent transcript)

DNAJB5-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.29016548).

BS2

High AC in GnomAdExome4 at 21 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349723.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAJB5	NM_001349723.3	MANE Select	c.-175C>T	5_prime_UTR	Exon 1 of 5	NP_001336652.1	O75953-4
DNAJB5	NM_001135004.3		c.-120C>T	5_prime_UTR	Exon 1 of 5	NP_001128476.3	A0A7I2RN43
DNAJB5	NM_001349725.2		c.-117C>T	5_prime_UTR	Exon 1 of 5	NP_001336654.2	A0A7I2RN43

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAJB5	ENST00000682809.1	MANE Select	c.-175C>T	5_prime_UTR	Exon 1 of 5	ENSP00000507741.1	O75953-4
DNAJB5	ENST00000312316.9	TSL:1	c.-77C>T	5_prime_UTR	Exon 1 of 4	ENSP00000312517.5	O75953-3
DNAJB5	ENST00000453597.8	TSL:2	c.-120C>T	5_prime_UTR	Exon 1 of 5	ENSP00000404079.4	A0A7I2RN43

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

AF XY:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000195

AC:

AN:

1079232

Hom.:

Cov.:

AF XY:

0.0000255

AC XY:

AN XY:

509588

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22924

American (AMR)

AF:

0.00

AC:

AN:

8406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14356

East Asian (EAS)

AF:

0.00

AC:

AN:

26494

South Asian (SAS)

AF:

0.00

AC:

AN:

19692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2912

European-Non Finnish (NFE)

AF:

0.0000217

AC:

AN:

919712

Other (OTH)

AF:

0.0000229

AC:

AN:

43626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

0.089

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.91

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.61

PhyloP100

0.80

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.050

REVEL

Benign

0.0050

Sift

Uncertain

0.026

Sift4G

Pathogenic

0.0

Vest4

0.16

MutPred

0.31

Loss of methylation at R41 (P = 0.0079)

MVP

0.72

MPC

1.0

ClinPred

0.40

GERP RS

3.0

PromoterAI

0.032

Neutral

(source)

gMVP

0.20

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over