chr3-180984706-T-G
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_145261.4(DNAJC19):āc.285A>Cā(p.Gly95=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,604,598 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0045 ( 4 hom., cov: 32)
Exomes š: 0.0045 ( 29 hom. )
Consequence
DNAJC19
NM_145261.4 synonymous
NM_145261.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.67
Genes affected
DNAJC19 (HGNC:30528): (DnaJ heat shock protein family (Hsp40) member C19) The protein encoded by this gene is thought to be part of a complex involved in the ATP-dependent transport of transit peptide-containing proteins from the inner cell membrane to the mitochondrial matrix. Defects in this gene are a cause of 3-methylglutaconic aciduria type 5 (MGA5), also known as dilated cardiomyopathy with ataxia (DCMA). Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1, 2, 6, 10, 14 and 19. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant 3-180984706-T-G is Benign according to our data. Variant chr3-180984706-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 137121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.67 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00452 (688/152188) while in subpopulation NFE AF= 0.00678 (461/68018). AF 95% confidence interval is 0.00627. There are 4 homozygotes in gnomad4. There are 335 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAJC19 | NM_145261.4 | c.285A>C | p.Gly95= | synonymous_variant | 6/6 | ENST00000382564.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAJC19 | ENST00000382564.8 | c.285A>C | p.Gly95= | synonymous_variant | 6/6 | 1 | NM_145261.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00452 AC: 688AN: 152070Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00489 AC: 1192AN: 243624Hom.: 5 AF XY: 0.00476 AC XY: 627AN XY: 131732
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GnomAD4 exome AF: 0.00450 AC: 6538AN: 1452410Hom.: 29 Cov.: 28 AF XY: 0.00454 AC XY: 3280AN XY: 722596
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GnomAD4 genome AF: 0.00452 AC: 688AN: 152188Hom.: 4 Cov.: 32 AF XY: 0.00450 AC XY: 335AN XY: 74422
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 04, 2013 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 22, 2020 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | DNAJC19: BP4, BS2 - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 24, 2016 | - - |
3-methylglutaconic aciduria type 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
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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