rs189308547
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2
The NM_025219.3(DNAJC5):c.75C>T(p.Asn25=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000083 in 1,614,076 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000081 ( 1 hom. )
Consequence
DNAJC5
NM_025219.3 synonymous
NM_025219.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.09
Genes affected
DNAJC5 (HGNC:16235): (DnaJ heat shock protein family (Hsp40) member C5) This gene is a member of the J protein family. J proteins function in many cellular processes by regulating the ATPase activity of 70 kDa heat shock proteins. The encoded protein plays a role in membrane trafficking and protein folding, and has been shown to have anti-neurodegenerative properties. The encoded protein is known to play a role in cystic fibrosis and Huntington's disease. A pseudogene of this gene is located on the short arm of chromosome 8. [provided by RefSeq, Nov 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
Variant 20-63928420-C-T is Benign according to our data. Variant chr20-63928420-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 290991.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1, Likely_benign=2}.
BP7
?
Synonymous conserved (PhyloP=-1.09 with no splicing effect.
BS2
?
High AC in GnomAd4 at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAJC5 | NM_025219.3 | c.75C>T | p.Asn25= | synonymous_variant | 2/5 | ENST00000360864.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAJC5 | ENST00000360864.9 | c.75C>T | p.Asn25= | synonymous_variant | 2/5 | 1 | NM_025219.3 | P1 | |
DNAJC5 | ENST00000470551.1 | c.75C>T | p.Asn25= | synonymous_variant, NMD_transcript_variant | 2/6 | 2 | |||
DNAJC5 | ENST00000703637.1 | c.75C>T | p.Asn25= | synonymous_variant, NMD_transcript_variant | 2/6 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152202Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000167 AC: 42AN: 251338Hom.: 0 AF XY: 0.000169 AC XY: 23AN XY: 135872
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GnomAD4 exome AF: 0.0000807 AC: 118AN: 1461756Hom.: 1 Cov.: 31 AF XY: 0.0000908 AC XY: 66AN XY: 727158
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152320Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74482
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 22, 2016 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 10, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 09, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Neuronal ceroid lipofuscinosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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