chr13-43023841-C-A

Variant names:

• chr13-43023841-C-A
• rs2281778
• NM_013238.3:c.108+107C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013238.3(DNAJC15):​c.108+107C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000011 in 912,252 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: DNAJC15 NM_013238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 16 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC15	NM_013238.3	c.108+107C>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+107C>A		intron_variant	Intron 1 of 5	1	NM_013238.3	ENSP00000368523.2
DNAJC15	ENST00000474320.1	n.532+107C>A		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000110 AC: 1 AN: 912252 Hom.: 0 AF XY: 0.00000218 AC XY: 1 AN XY: 457828

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21950

American (AMR) AF: 0.00 AC: 0 AN: 28500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18888

East Asian (EAS) AF: 0.00 AC: 0 AN: 33176

South Asian (SAS) AF: 0.00 AC: 0 AN: 62184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4648

European-Non Finnish (NFE) AF: 0.00000150 AC: 1 AN: 668428

Other (OTH) AF: 0.00 AC: 0 AN: 42010

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.5
DANN	Benign	0.49
PhyloP100		0.049
PromoterAI		-0.038	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2281778; hg19: chr13-43597977;