3-180984096-T-TAC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145261.4(DNAJC19):c.*543_*544insGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000347 in 446,562 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (0 hom.)
• Consequence: DNAJC19 NM_145261.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.488

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC19	NM_145261.4	c.*543_*544insGT		3_prime_UTR_variant	6/6	ENST00000382564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC19	ENST00000382564.8	c.*543_*544insGT		3_prime_UTR_variant	6/6	1	NM_145261.4	P1
DNAJC19	ENST00000688055.1	c.*1821_*1822insGT		3_prime_UTR_variant	5/5
DNAJC19	ENST00000482363.2	n.3007_3008insGT		non_coding_transcript_exon_variant	4/4	2
DNAJC19	ENST00000469657.5	c.*670_*671insGT		3_prime_UTR_variant, NMD_transcript_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.000218 AC: 33 AN: 151136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.000869

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.000834

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.000481

GnomAD3 exomes AF: 0.000486 AC: 48 AN: 98818 Hom.: 0 AF XY: 0.000580 AC XY: 31 AN XY: 53476

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.00112

Gnomad EAS exome AF: 0.000251

Gnomad SAS exome AF: 0.00117

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000373

Gnomad OTH exome AF: 0.000319

GnomAD4 exome AF: 0.000413 AC: 122 AN: 295324 Hom.: 0 Cov.: 0 AF XY: 0.000446 AC XY: 75 AN XY: 168142

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000186

Gnomad4 ASJ exome AF: 0.00123

Gnomad4 EAS exome AF: 0.000222

Gnomad4 SAS exome AF: 0.000805

Gnomad4 FIN exome AF: 0.0000828

Gnomad4 NFE exome AF: 0.000329

Gnomad4 OTH exome AF: 0.000218

GnomAD4 genome AF: 0.000218 AC: 33 AN: 151238 Hom.: 0 Cov.: 32 AF XY: 0.000271 AC XY: 20 AN XY: 73916

Gnomad4 AFR AF: 0.000242

Gnomad4 AMR AF: 0.0000659

Gnomad4 ASJ AF: 0.000869

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.000836

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.000476

Bravo AF: 0.000193

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

3-methylglutaconic aciduria type 5 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs148074891; hg19: chr3-180701884;