dbSNP rs5758111: DNAJB7:c.*389T>C (chr22-40860676-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145174.2(DNAJB7):c.*389T>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 0.00151 in 1,218,696 control chromosomes in the GnomAD database, including 46 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 0.0026 ( 17 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 29 hom. )

Consequence

DNAJB7
NM_145174.2 3_prime_UTR

Scores

Splicing: ADA: 0.00001992

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0960

Publications

1 publications found

Variant links:

Genes affected

DNAJB7 (HGNC:24986): (DnaJ heat shock protein family (Hsp40) member B7) The protein encoded by this intronless gene belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJ proteins may have up to 3 distinct domains: a conserved 70-amino acid J domain, usually at the N terminus; a glycine/phenylalanine (G/F)-rich region; and a cysteine-rich domain containing 4 motifs resembling a zinc finger domain.[provided by RefSeq, Mar 2011]

DNAJB7 links:

XPNPEP3 (HGNC:28052): (X-prolyl aminopeptidase 3) The protein encoded by this gene belongs to the family of X-pro-aminopeptidases that utilize a metal cofactor, and remove the N-terminal amino acid from peptides with a proline residue in the penultimate position. This protein has been shown to localize to the mitochondria of renal cells, and have a role in ciliary function. Mutations in this gene are associated with nephronophthisis-like nephropathy-1. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene, however, expression of some of these isoforms in vivo is not known.[provided by RefSeq, Mar 2011]

XPNPEP3 Gene-Disease associations (from GenCC):

nephronophthisis-like nephropathy 1
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics
late-onset nephronophthisis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

XPNPEP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.851811).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DNAJB7	NM_145174.2 link	c.*389T>C	3_prime_UTR_variant	Exon 1 of 1	ENST00000307221.5	NP_660157.1	Q7Z6W7
XPNPEP3	NM_022098.4 link	c.64+3431A>G	intron_variant	Intron 1 of 9	ENST00000357137.9	NP_071381.1	Q9NQH7-1
XPNPEP3	NM_001204827.2 link	c.65-2A>G	splice_acceptor_variant, intron_variant	Intron 1 of 2		NP_001191756.1	A0A087X0Z2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB7	ENST00000307221.5 link	c.*389T>C		3_prime_UTR_variant	Exon 1 of 1	6	NM_145174.2	ENSP00000307197.4		Q7Z6W7
XPNPEP3	ENST00000357137.9 link	c.64+3431A>G		intron_variant	Intron 1 of 9	1	NM_022098.4	ENSP00000349658.4		Q9NQH7-1

Frequencies

GnomAD3 genomes

AF:

0.00258

AC:

390

AN:

151348

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000680

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00184

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0571

Gnomad SAS

AF:

0.00437

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00352

AC:

329

AN:

93542

AF XY:

0.00318

show subpopulations

Gnomad AFR exome

AF:

0.000441

Gnomad AMR exome

AF:

0.000269

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0424

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00553

GnomAD4 exome

AF:

0.00136

AC:

1456

AN:

1067230

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

714

AN XY:

535728

show subpopulations

African (AFR)

AF:

0.000389

AC:

AN:

23140

American (AMR)

AF:

0.000195

AC:

AN:

25612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21758

East Asian (EAS)

AF:

0.0293

AC:

954

AN:

32570

South Asian (SAS)

AF:

0.00181

AC:

114

AN:

62840

European-Finnish (FIN)

AF:

0.0000310

AC:

AN:

32286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4688

European-Non Finnish (NFE)

AF:

0.0000318

AC:

AN:

817798

Other (OTH)

AF:

0.00746

AC:

347

AN:

46538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

133

200

266

333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00257

AC:

389

AN:

151466

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

206

AN XY:

74010

show subpopulations

African (AFR)

AF:

0.000678

AC:

AN:

41274

American (AMR)

AF:

0.00184

AC:

AN:

15200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0571

AC:

294

AN:

5152

South Asian (SAS)

AF:

0.00416

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67876

Other (OTH)

AF:

0.00711

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.000856

Hom.:

Bravo

AF:

0.00238

ExAC

AF:

0.00195

AC:

Asia WGS

AF:

0.0380

AC:

133

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.1

(source)

DANN

Benign

0.54

FATHMM_MKL

Benign

0.0093

PhyloP100

0.096

GERP RS

-0.33

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0020

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over