NM_013238.3:c.108+542G>A

Variant names:

• chr13-43024276-G-A
• rs9594865
• NM_013238.3:c.108+542G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013238.3(DNAJC15):​c.108+542G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,244 control chromosomes in the GnomAD database, including 3,768 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3768 hom., cov: 30)
• Consequence: DNAJC15 NM_013238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497
• Publications: 10 publications found

Genes affected

DNAJC15 (HGNC:20325): (DnaJ heat shock protein family (Hsp40) member C15) Predicted to enable ATPase activator activity. Predicted to be involved in protein import into mitochondrial matrix. Predicted to act upstream of or within several processes, including cellular response to starvation; negative regulation of mitochondrial electron transport, NADH to ubiquinone; and negative regulation of protein-containing complex assembly. Predicted to be located in mitochondrial inner membrane. Predicted to be part of PAM complex, Tim23 associated import motor. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC15	NM_013238.3	c.108+542G>A		intron_variant	Intron 1 of 5	ENST00000379221.4	NP_037370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC15	ENST00000379221.4	c.108+542G>A		intron_variant	Intron 1 of 5	1	NM_013238.3	ENSP00000368523.2
DNAJC15	ENST00000474320.1	n.532+542G>A		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33544 AN: 151136 Hom.: 3762 Cov.: 30

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0888

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.217

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.222 AC: 33577 AN: 151244 Hom.: 3768 Cov.: 30 AF XY: 0.218 AC XY: 16090 AN XY: 73814

African (AFR) AF: 0.224 AC: 9200 AN: 41122

American (AMR) AF: 0.184 AC: 2804 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 761 AN: 3464

East Asian (EAS) AF: 0.0892 AC: 459 AN: 5146

South Asian (SAS) AF: 0.139 AC: 665 AN: 4792

European-Finnish (FIN) AF: 0.246 AC: 2534 AN: 10310

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.240 AC: 16325 AN: 67886

Other (OTH) AF: 0.219 AC: 458 AN: 2094

Alfa AF: 0.226 Hom.: 5302

Bravo AF: 0.218

Asia WGS AF: 0.140 AC: 489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.77
DANN	Benign	0.76
PhyloP100		-0.50
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: rs9594865; hg19: chr13-43598412;