chr3-180984643-T-C

Variant names:

• chr3-180984643-T-C
• rs771098271
• NM_145261.4:c.348A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_145261.4(DNAJC19):​c.348A>G​(p.Lys116Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAJC19 NM_145261.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.945
• 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 3-180984643-T-C is Benign according to our data. Variant chr3-180984643-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1640522.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.945 with no splicing effect.

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.348A>G	p.Lys116Lys	synonymous	Exon 6 of 6	NP_660304.1	A0A0S2Z5X1
	DNAJC19	NM_001190233.2		c.273A>G	p.Lys91Lys	synonymous	Exon 6 of 6	NP_001177162.1	Q96DA6-2
	DNAJC19	NR_033721.2		n.430A>G		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.348A>G	p.Lys116Lys	synonymous	Exon 6 of 6	ENSP00000372005.2	Q96DA6-1
	DNAJC19	ENST00000928270.1		c.345A>G	p.Lys115Lys	synonymous	Exon 6 of 6	ENSP00000598329.1
	DNAJC19	ENST00000479269.5	TSL:3	c.273A>G	p.Lys91Lys	synonymous	Exon 6 of 6	ENSP00000419191.1	Q96DA6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000824 AC: 2 AN: 242622 AF XY: 0.0000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000553

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447968 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 720560

African (AFR) AF: 0.00 AC: 0 AN: 33112

American (AMR) AF: 0.00 AC: 0 AN: 44172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25820

East Asian (EAS) AF: 0.00 AC: 0 AN: 39390

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5126

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102270

Other (OTH) AF: 0.00 AC: 0 AN: 59782

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	3-methylglutaconic aciduria type 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.8
DANN	Benign	0.80
PhyloP100		0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs771098271; hg19: chr3-180702431;