Variant chr3-180989631-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_145261.4(DNAJC19):c.-29G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,584,672 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 9 hom. )

Consequence

DNAJC19
NM_145261.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.961

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 3-180989631-C-A is Benign according to our data. Variant chr3-180989631-C-A is described in ClinVar as [Benign]. Clinvar id is 137122.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00141 (214/152218) while in subpopulation NFE AF= 0.00275 (187/68008). AF 95% confidence interval is 0.00243. There are 0 homozygotes in gnomad4. There are 96 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC19	NM_145261.4 linkuse as main transcript	c.-29G>T		5_prime_UTR_variant	1/6	ENST00000382564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC19	ENST00000382564.8 linkuse as main transcript	c.-29G>T		5_prime_UTR_variant	1/6	1	NM_145261.4	P1	Q96DA6-1

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

214

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00275

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00129

AC:

254

AN:

196502

Hom.:

AF XY:

0.00122

AC XY:

129

AN XY:

106130

show subpopulations

Gnomad AFR exome

AF:

0.000520

Gnomad AMR exome

AF:

0.0000680

Gnomad ASJ exome

AF:

0.000112

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.000829

Gnomad NFE exome

AF:

0.00235

Gnomad OTH exome

AF:

0.000784

GnomAD4 exome

AF:

0.00251

AC:

3601

AN:

1432454

Hom.:

Cov.:

AF XY:

0.00245

AC XY:

1740

AN XY:

709738

show subpopulations

Gnomad4 AFR exome

AF:

0.000394

Gnomad4 AMR exome

AF:

0.0000739

Gnomad4 ASJ exome

AF:

0.000118

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00130

Gnomad4 FIN exome

AF:

0.000675

Gnomad4 NFE exome

AF:

0.00307

Gnomad4 OTH exome

AF:

0.00120

GnomAD4 genome

AF:

0.00141

AC:

214

AN:

152218

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00275

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000539

Hom.:

Bravo

AF:

0.00134

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 14, 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. -

DNAJC19-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 27, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.6

DANN

Benign

0.81

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over