1-6640071-CAAAAAA-CAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018198.4(DNAJC11):c.1098-18_1098-15del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,217,382 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000024 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: DNAJC11 NM_018198.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

Genes affected

DNAJC11 (HGNC:25570): (DnaJ heat shock protein family (Hsp40) member C11) Involved in cristae formation. Located in mitochondrial outer membrane and nuclear speck. Part of MIB complex. Colocalizes with MICOS complex and SAM complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC11	NM_018198.4	c.1098-18_1098-15del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000377577.10
DNAJC11	XM_047424842.1	c.828-18_828-15del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC11	ENST00000377577.10	c.1098-18_1098-15del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_018198.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000242 AC: 2 AN: 82512 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000189 AC: 214 AN: 1134870 Hom.: 0 AF XY: 0.000212 AC XY: 116 AN XY: 547658

Gnomad4 AFR exome AF: 0.000166

Gnomad4 AMR exome AF: 0.000719

Gnomad4 ASJ exome AF: 0.000326

Gnomad4 EAS exome AF: 0.000439

Gnomad4 SAS exome AF: 0.000180

Gnomad4 FIN exome AF: 0.000614

Gnomad4 NFE exome AF: 0.000151

Gnomad4 OTH exome AF: 0.000372

GnomAD4 genome AF: 0.0000242 AC: 2 AN: 82512 Hom.: 0 Cov.: 0 AF XY: 0.0000521 AC XY: 2 AN XY: 38370

Gnomad4 AFR AF: 0.000100

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs56145914; hg19: chr1-6700131;