1-6640071-CAAAAAA-CAAA

Variant names:

• chr1-6640071-CAAA-C
• rs56145914
• NM_018198.4:c.1098-17_1098-15delTTT

Variant summary

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

The NM_018198.4(DNAJC11):​c.1098-17_1098-15delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,212,668 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0012 (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.1098-17_1098-15delTTT		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.1098-17_1098-15delTTT		intron	N/A	ENSP00000366800.5	Q9NVH1-1
	DNAJC11	ENST00000294401.11	TSL:1	c.1098-1710_1098-1708delTTT		intron	N/A	ENSP00000294401.7	Q9NVH1-3
	DNAJC11	ENST00000451196.5	TSL:1	c.741-5290_741-5288delTTT		intron	N/A	ENSP00000415871.1	Q5TH61

Frequencies

GnomAD3 genomes AF: 0.0000485 AC: 4 AN: 82514 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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000957

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00549 AC: 145 AN: 26422 AF XY: 0.00528

Gnomad AFR exome AF: 0.00366

Gnomad AMR exome AF: 0.00636

Gnomad ASJ exome AF: 0.00884

Gnomad EAS exome AF: 0.00418

Gnomad FIN exome AF: 0.00437

Gnomad NFE exome AF: 0.00656

Gnomad OTH exome AF: 0.00355

GnomAD4 exome AF: 0.00118 AC: 1336 AN: 1130182 Hom.: 0 AF XY: 0.00122 AC XY: 665 AN XY: 545344

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

African (AFR) AF: 0.00204 AC: 49 AN: 24008

American (AMR) AF: 0.00442 AC: 67 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00269 AC: 41 AN: 15252

East Asian (EAS) AF: 0.00243 AC: 66 AN: 27166

South Asian (SAS) AF: 0.00119 AC: 59 AN: 49664

European-Finnish (FIN) AF: 0.00347 AC: 84 AN: 24196

Middle Eastern (MID) AF: 0.00198 AC: 6 AN: 3036

European-Non Finnish (NFE) AF: 0.000953 AC: 883 AN: 926166

Other (OTH) AF: 0.00178 AC: 81 AN: 45520

⚠️ 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: 0.0000485 AC: 4 AN: 82486 Hom.: 0 Cov.: 0 AF XY: 0.0000782 AC XY: 3 AN XY: 38378

⚠️ 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: 20012

American (AMR) AF: 0.00 AC: 0 AN: 7290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3234

South Asian (SAS) AF: 0.00 AC: 0 AN: 2918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3146

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

European-Non Finnish (NFE) AF: 0.0000957 AC: 4 AN: 41792

Other (OTH) AF: 0.00 AC: 0 AN: 1130

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0431739), which strongly suggests a high chance of mosaicism in these individuals.

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

Other links and lift over

dbSNP: rs56145914; hg19: chr1-6700131;