1-6640071-CAAAAAA-CAAA

Position:

• chr1-6640071-CAAAAAA-CAAA

Variant summary

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

The NM_018198.4(DNAJC11):​c.1098-17_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 0.00111 in 1,212,668 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 0.000048 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0012 (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.1098-17_1098-15del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000377577.10
DNAJC11	XM_047424842.1	c.828-17_828-15del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC11	ENST00000377577.10	c.1098-17_1098-15del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_018198.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000485 AC: 4 AN: 82514 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.0000957

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00549 AC: 145 AN: 26422 Hom.: 0 AF XY: 0.00528 AC XY: 70 AN XY: 13270

Gnomad AFR exome AF: 0.00366

Gnomad AMR exome AF: 0.00636

Gnomad ASJ exome AF: 0.00884

Gnomad EAS exome AF: 0.00418

Gnomad SAS exome AF: 0.00373

Gnomad FIN exome AF: 0.00437

Gnomad NFE exome AF: 0.00656

Gnomad OTH exome AF: 0.00355

GnomAD4 exome AF: 0.00118 AC: 1336 AN: 1130182 Hom.: 0 AF XY: 0.00122 AC XY: 665 AN XY: 545344

Gnomad4 AFR exome AF: 0.00204

Gnomad4 AMR exome AF: 0.00442

Gnomad4 ASJ exome AF: 0.00269

Gnomad4 EAS exome AF: 0.00243

Gnomad4 SAS exome AF: 0.00119

Gnomad4 FIN exome AF: 0.00347

Gnomad4 NFE exome AF: 0.000953

Gnomad4 OTH exome AF: 0.00178

GnomAD4 genome AF: 0.0000485 AC: 4 AN: 82486 Hom.: 0 Cov.: 0 AF XY: 0.0000782 AC XY: 3 AN XY: 38378

Gnomad4 AFR AF: 0.00

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: 0.0000957

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;