1-6640071-CAAAAAA-CAAAAAAAAAAAAA

Variant names:

• chr1-6640071-C-CAAAAAAA
• rs56145914
• NM_018198.4:c.1098-21_1098-15dupTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018198.4(DNAJC11):​c.1098-21_1098-15dupTTTTTTT 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 0.000048 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000044 (0 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: Uncertain_significance. The variant received 0 ACMG points.

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.1098-21_1098-15dupTTTTTTT		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.1098-15_1098-14insTTTTTTT		intron	N/A	ENSP00000366800.5	Q9NVH1-1
	DNAJC11	ENST00000294401.11	TSL:1	c.1098-1708_1098-1707insTTTTTTT		intron	N/A	ENSP00000294401.7	Q9NVH1-3
	DNAJC11	ENST00000451196.5	TSL:1	c.741-5288_741-5287insTTTTTTT		intron	N/A	ENSP00000415871.1	Q5TH61

Frequencies

GnomAD3 genomes AF: 0.0000485 AC: 4 AN: 82518 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000318

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000478

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000440 AC: 5 AN: 1136528 Hom.: 0 Cov.: 0 AF XY: 0.00000365 AC XY: 2 AN XY: 548494

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

African (AFR) AF: 0.00 AC: 0 AN: 24168

American (AMR) AF: 0.00 AC: 0 AN: 15368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15364

East Asian (EAS) AF: 0.00 AC: 0 AN: 27428

South Asian (SAS) AF: 0.0000400 AC: 2 AN: 50048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3046

European-Non Finnish (NFE) AF: 0.00000215 AC: 2 AN: 930788

Other (OTH) AF: 0.0000218 AC: 1 AN: 45806

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000451865), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000485 AC: 4 AN: 82518 Hom.: 0 Cov.: 0 AF XY: 0.0000782 AC XY: 3 AN XY: 38374

African (AFR) AF: 0.00 AC: 0 AN: 19990

American (AMR) AF: 0.000137 AC: 1 AN: 7286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2386

East Asian (EAS) AF: 0.00 AC: 0 AN: 3250

South Asian (SAS) AF: 0.00 AC: 0 AN: 2936

European-Finnish (FIN) AF: 0.000318 AC: 1 AN: 3144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 186

European-Non Finnish (NFE) AF: 0.0000478 AC: 2 AN: 41808

Other (OTH) AF: 0.00 AC: 0 AN: 1118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56145914; hg19: chr1-6700131;