1-6640071-CAAAAAA-CAAAAAAAA

Position:

• chr1-6640071-CAAAAAA-CAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_018198.4(DNAJC11):​c.1098-15_1098-14insTT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 0)
  • Exomes 𝑓: 0.012 (3 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0124 (14013/1127456) while in subpopulation SAS AF= 0.0314 (1563/49698). AF 95% confidence interval is 0.0302. There are 3 homozygotes in gnomad4_exome. There are 7132 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC11	NM_018198.4	c.1098-15_1098-14insTT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000377577.10
DNAJC11	XM_047424842.1	c.828-15_828-14insTT		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC11	ENST00000377577.10	c.1098-15_1098-14insTT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_018198.4	P1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 155 AN: 82494 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.000419

Gnomad EAS AF: 0.00338

Gnomad SAS AF: 0.00647

Gnomad FIN AF: 0.000954

Gnomad MID AF: 0.00538

Gnomad NFE AF: 0.00153

Gnomad OTH AF: 0.000894

GnomAD3 exomes AF: 0.0331 AC: 874 AN: 26422 Hom.: 1 AF XY: 0.0342 AC XY: 454 AN XY: 13270

Gnomad AFR exome AF: 0.0286

Gnomad AMR exome AF: 0.0316

Gnomad ASJ exome AF: 0.0404

Gnomad EAS exome AF: 0.0376

Gnomad SAS exome AF: 0.0479

Gnomad FIN exome AF: 0.0102

Gnomad NFE exome AF: 0.0291

Gnomad OTH exome AF: 0.0379

GnomAD4 exome AF: 0.0124 AC: 14013 AN: 1127456 Hom.: 3 Cov.: 0 AF XY: 0.0131 AC XY: 7132 AN XY: 544216

Gnomad4 AFR exome AF: 0.0114

Gnomad4 AMR exome AF: 0.0198

Gnomad4 ASJ exome AF: 0.0179

Gnomad4 EAS exome AF: 0.0215

Gnomad4 SAS exome AF: 0.0314

Gnomad4 FIN exome AF: 0.0162

Gnomad4 NFE exome AF: 0.0108

Gnomad4 OTH exome AF: 0.0136

GnomAD4 genome AF: 0.00188 AC: 155 AN: 82466 Hom.: 2 Cov.: 0 AF XY: 0.00219 AC XY: 84 AN XY: 38376

Gnomad4 AFR AF: 0.00125

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.000419

Gnomad4 EAS AF: 0.00340

Gnomad4 SAS AF: 0.00651

Gnomad4 FIN AF: 0.000954

Gnomad4 NFE AF: 0.00153

Gnomad4 OTH AF: 0.000885

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;