1-6640071-CAAAAAA-CAAAAA

Variant names:

• chr1-6640071-CA-C
• rs56145914
• NM_018198.4:c.1098-15delT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_018198.4(DNAJC11):​c.1098-15delT variant causes a 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 0.0084 (1 hom., cov: 0)
  • Exomes 𝑓: 0.14 (2 hom.)
• Consequence: DNAJC11 NM_018198.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018198.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC11	NM_018198.4	MANE Select	c.1098-15delT		intron	N/A	NP_060668.2	Q9NVH1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC11	ENST00000377577.10	TSL:1 MANE Select	c.1098-15delT		intron	N/A	ENSP00000366800.5	Q9NVH1-1
	DNAJC11	ENST00000294401.11	TSL:1	c.1098-1708delT		intron	N/A	ENSP00000294401.7	Q9NVH1-3
	DNAJC11	ENST00000451196.5	TSL:1	c.741-5288delT		intron	N/A	ENSP00000415871.1	Q5TH61

Frequencies

GnomAD3 genomes AF: 0.00842 AC: 695 AN: 82502 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0290

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.000838

Gnomad EAS AF: 0.000923

Gnomad SAS AF: 0.000681

Gnomad FIN AF: 0.00828

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00667

Gnomad OTH AF: 0.00804

GnomAD2 exomes AF: 0.202 AC: 5347 AN: 26422 AF XY: 0.198

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.175

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.137 AC: 145169 AN: 1062594 Hom.: 2 Cov.: 0 AF XY: 0.136 AC XY: 70005 AN XY: 513102

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

African (AFR) AF: 0.168 AC: 3784 AN: 22534

American (AMR) AF: 0.183 AC: 2703 AN: 14810

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 2359 AN: 14734

East Asian (EAS) AF: 0.166 AC: 4387 AN: 26428

South Asian (SAS) AF: 0.100 AC: 4796 AN: 47936

European-Finnish (FIN) AF: 0.208 AC: 4926 AN: 23630

Middle Eastern (MID) AF: 0.143 AC: 412 AN: 2890

European-Non Finnish (NFE) AF: 0.133 AC: 115350 AN: 866454

Other (OTH) AF: 0.149 AC: 6452 AN: 43178

⚠️ 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 AF: 0.00844 AC: 696 AN: 82474 Hom.: 1 Cov.: 0 AF XY: 0.00860 AC XY: 330 AN XY: 38372

African (AFR) AF: 0.0160 AC: 321 AN: 20008

American (AMR) AF: 0.00576 AC: 42 AN: 7290

Ashkenazi Jewish (ASJ) AF: 0.000838 AC: 2 AN: 2386

East Asian (EAS) AF: 0.000928 AC: 3 AN: 3234

South Asian (SAS) AF: 0.000685 AC: 2 AN: 2918

European-Finnish (FIN) AF: 0.00828 AC: 26 AN: 3140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 164

European-Non Finnish (NFE) AF: 0.00668 AC: 279 AN: 41788

Other (OTH) AF: 0.00795 AC: 9 AN: 1132

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs56145914; hg19: chr1-6700131;