22-40861798-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_145174.2(DNAJB7):c.197A>G(p.Asp66Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
DNAJB7
NM_145174.2 missense
NM_145174.2 missense
Scores
9
8
2
Clinical Significance
Conservation
PhyloP100: 0.917
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]
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.859
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAJB7 | NM_145174.2 | c.197A>G | p.Asp66Gly | missense_variant | 1/1 | ENST00000307221.5 | |
XPNPEP3 | NM_022098.4 | c.64+4553T>C | intron_variant | ENST00000357137.9 | |||
XPNPEP3 | NM_001204827.2 | c.*193T>C | 3_prime_UTR_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAJB7 | ENST00000307221.5 | c.197A>G | p.Asp66Gly | missense_variant | 1/1 | NM_145174.2 | P1 | ||
XPNPEP3 | ENST00000357137.9 | c.64+4553T>C | intron_variant | 1 | NM_022098.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250566Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135468
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461160Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 726896
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74444
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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 | Ambry Genetics | Nov 30, 2022 | The c.197A>G (p.D66G) alteration is located in exon 1 (coding exon 1) of the DNAJB7 gene. This alteration results from a A to G substitution at nucleotide position 197, causing the aspartic acid (D) at amino acid position 66 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
T
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at