3-180988083-CAA-GAG

Variant names:

• chr3-180988083-CAA-GAG
• NM_145261.4:c.67_69delTTGinsCTC
• DNAJC19 p.24

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_145261.4(DNAJC19):​c.67_69delTTGinsCTC​(p.24) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L23L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJC19 NM_145261.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.47
• Publications: 0 publications found

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]

DNAJC19 Gene-Disease associations (from GenCC):

• 3-methylglutaconic aciduria type 5

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145261.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC19	NM_145261.4	MANE Select	c.67_69delTTGinsCTC	p.24	synonymous	N/A	NP_660304.1	A0A0S2Z5X1
	DNAJC19	NM_001190233.2		c.-9_-7delTTGinsCTC		5_prime_UTR	Exon 3 of 6	NP_001177162.1	Q96DA6-2
	DNAJC19	NR_033721.2		n.149_151delTTGinsCTC		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC19	ENST00000382564.8	TSL:1 MANE Select	c.67_69delTTGinsCTC	p.24	synonymous	N/A	ENSP00000372005.2	Q96DA6-1
	DNAJC19	ENST00000928270.1		c.67_69delTTGinsCTC	p.24	synonymous	N/A	ENSP00000598329.1
	DNAJC19	ENST00000688055.1		c.67_69delTTGinsCTC	p.24	synonymous	N/A	ENSP00000508688.1	A0A8I5KQT8

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-180705871;