Genetic Variant DNAJB7:p.Asp215Asn (chr22-40861352-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145174.2(DNAJB7):c.643G>A(p.Asp215Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DNAJB7
NM_145174.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.559

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.106285065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB7	NM_145174.2 link	c.643G>A	p.Asp215Asn	missense_variant	Exon 1 of 1	ENST00000307221.5	NP_660157.1	Q7Z6W7
XPNPEP3	NM_022098.4 link	c.64+4107C>T		intron_variant	Intron 1 of 9	ENST00000357137.9	NP_071381.1	Q9NQH7-1
XPNPEP3	NM_001204827.2 link	c.*13-266C>T		intron_variant	Intron 2 of 2		NP_001191756.1	A0A087X0Z2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB7	ENST00000307221.5 link	c.643G>A	p.Asp215Asn	missense_variant	Exon 1 of 1	6	NM_145174.2	ENSP00000307197.4		Q7Z6W7
XPNPEP3	ENST00000357137.9 link	c.64+4107C>T		intron_variant	Intron 1 of 9	1	NM_022098.4	ENSP00000349658.4		Q9NQH7-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.018

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.1

REVEL

Benign

0.064

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.027

Vest4

0.21

MutPred

0.32

Gain of disorder (P = 0.1852);

MVP

0.64

MPC

0.032

ClinPred

0.70

GERP RS

2.2

Varity_R

0.16

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over