3-180984452-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145261.4(DNAJC19):c.*188G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 615,418 control chromosomes in the GnomAD database, including 15,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4620 hom., cov: 32)
  • Exomes 𝑓: 0.21 (10994 hom.)
• Consequence: DNAJC19 NM_145261.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.627

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-180984452-C-T is Benign according to our data. Variant chr3-180984452-C-T is described in ClinVar as [Benign]. Clinvar id is 1253152.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC19	NM_145261.4	c.*188G>A		3_prime_UTR_variant	6/6	ENST00000382564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC19	ENST00000382564.8	c.*188G>A		3_prime_UTR_variant	6/6	1	NM_145261.4	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36499 AN: 151926 Hom.: 4595 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.261

GnomAD3 exomes AF: 0.209 AC: 30227 AN: 144560 Hom.: 3315 AF XY: 0.211 AC XY: 16449 AN XY: 77888

Gnomad AFR exome AF: 0.311

Gnomad AMR exome AF: 0.155

Gnomad ASJ exome AF: 0.301

Gnomad EAS exome AF: 0.159

Gnomad SAS exome AF: 0.227

Gnomad FIN exome AF: 0.157

Gnomad NFE exome AF: 0.221

Gnomad OTH exome AF: 0.230

GnomAD4 exome AF: 0.211 AC: 97937 AN: 463374 Hom.: 10994 Cov.: 4 AF XY: 0.213 AC XY: 53948 AN XY: 252900

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.241 AC: 36567 AN: 152044 Hom.: 4620 Cov.: 32 AF XY: 0.236 AC XY: 17512 AN XY: 74328

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.268

Alfa AF: 0.237 Hom.: 1562

Bravo AF: 0.247

Asia WGS AF: 0.246 AC: 856 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.0
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1051411; hg19: chr3-180702240;