1-6640071-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018198.4(DNAJC11):c.1098-15_1098-14insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (6434 hom., cov: 0)
  • Exomes 𝑓: 0.20 (300 hom.)
• Consequence: DNAJC11 NM_018198.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 1-6640071-C-CA is Benign according to our data. Variant chr1-6640071-C-CA is described in ClinVar as [Benign]. Clinvar id is 402790.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.466 AC: 38439 AN: 82518 Hom.: 6442 Cov.: 0

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.475

GnomAD3 exomes AF: 0.173 AC: 4575 AN: 26422 Hom.: 52 AF XY: 0.176 AC XY: 2340 AN XY: 13270

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.214

Gnomad SAS exome AF: 0.224

Gnomad FIN exome AF: 0.0845

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.204 AC: 225843 AN: 1106338 Hom.: 300 Cov.: 0 AF XY: 0.204 AC XY: 108782 AN XY: 533998

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.239

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.201

GnomAD4 genome AF: 0.466 AC: 38409 AN: 82490 Hom.: 6434 Cov.: 0 AF XY: 0.465 AC XY: 17866 AN XY: 38396

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.473

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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;