1-6640071-CAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr1-6640071-C-CAAAAAAAAAAAAAAAAA
• rs56145914
• NM_018198.4:c.1098-31_1098-15dupTTTTTTTTTTTTTTTTT

Variant summary

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

The NM_018198.4(DNAJC11):​c.1098-31_1098-15dupTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000012 (0 hom., cov: 0)
• 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.1098-31_1098-15dupTTTTTTTTTTTTTTTTT		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_1098-14insTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000366800.5	Q9NVH1-1
	DNAJC11	ENST00000294401.11	TSL:1	c.1098-1708_1098-1707insTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000294401.7	Q9NVH1-3
	DNAJC11	ENST00000451196.5	TSL:1	c.741-5288_741-5287insTTTTTTTTTTTTTTTTT		intron	N/A	ENSP00000415871.1	Q5TH61

Frequencies

GnomAD3 genomes AF: 0.0000121 AC: 1 AN: 82520 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: 0.000318

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000121 AC: 1 AN: 82520 Hom.: 0 Cov.: 0 AF XY: 0.0000261 AC XY: 1 AN XY: 38374

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

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

American (AMR) AF: 0.00 AC: 0 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: 3148

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 41806

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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;