3-180984452-C-T

Variant names:

• chr3-180984452-C-T
• rs1051411
• NM_145261.4:c.*188G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.627
• Publications: 4 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1253152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

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.*188G>A		3_prime_UTR	Exon 6 of 6	NP_660304.1	A0A0S2Z5X1
	DNAJC19	NM_001190233.2		c.*188G>A		3_prime_UTR	Exon 6 of 6	NP_001177162.1	Q96DA6-2
	DNAJC19	NR_033721.2		n.621G>A		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC19	ENST00000382564.8	TSL:1 MANE Select	c.*188G>A		3_prime_UTR	Exon 6 of 6	ENSP00000372005.2	Q96DA6-1
	DNAJC19	ENST00000928270.1		c.*188G>A		3_prime_UTR	Exon 6 of 6	ENSP00000598329.1
	DNAJC19	ENST00000688055.1		c.*1466G>A		3_prime_UTR	Exon 5 of 5	ENSP00000508688.1	A0A8I5KQT8

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

GnomAD2 exomes AF: 0.209 AC: 30227 AN: 144560 AF XY: 0.211

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 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

African (AFR) AF: 0.306 AC: 4146 AN: 13532

American (AMR) AF: 0.161 AC: 5102 AN: 31740

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 5097 AN: 16676

East Asian (EAS) AF: 0.103 AC: 2497 AN: 24266

South Asian (SAS) AF: 0.225 AC: 13706 AN: 60858

European-Finnish (FIN) AF: 0.160 AC: 5482 AN: 34232

Middle Eastern (MID) AF: 0.256 AC: 486 AN: 1900

European-Non Finnish (NFE) AF: 0.218 AC: 55634 AN: 255754

Other (OTH) AF: 0.237 AC: 5787 AN: 24416

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

African (AFR) AF: 0.315 AC: 13067 AN: 41478

American (AMR) AF: 0.205 AC: 3134 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1022 AN: 3466

East Asian (EAS) AF: 0.147 AC: 762 AN: 5182

South Asian (SAS) AF: 0.230 AC: 1108 AN: 4814

European-Finnish (FIN) AF: 0.156 AC: 1646 AN: 10554

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14933 AN: 67970

Other (OTH) AF: 0.268 AC: 564 AN: 2108

Alfa AF: 0.237 Hom.: 1912

Bravo AF: 0.247

Asia WGS AF: 0.246 AC: 856 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.41
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1051411; hg19: chr3-180702240;