chr1-6640071-CAA-C

Variant names:

• chr1-6640071-CAA-C
• rs56145914
• NM_018198.4:c.1098-16_1098-15delTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018198.4(DNAJC11):​c.1098-16_1098-15delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,188,428 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 0.000049 (0 hom., cov: 0)
  • Exomes 𝑓: 0.013 (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 2 ACMG points.

• PM2: Variant has high frequency in the AMR (0.029) population. However there is too low homozygotes in high coverage region: (expected more than 41, got 0).

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.1098-16_1098-15delTT		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.1098-16_1098-15delTT		intron	N/A	ENSP00000366800.5	Q9NVH1-1
	DNAJC11	ENST00000294401.11	TSL:1	c.1098-1709_1098-1708delTT		intron	N/A	ENSP00000294401.7	Q9NVH1-3
	DNAJC11	ENST00000451196.5	TSL:1	c.741-5289_741-5288delTT		intron	N/A	ENSP00000415871.1	Q5TH61

Frequencies

GnomAD3 genomes AF: 0.0000485 AC: 4 AN: 82480 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000500

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000479

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0316 AC: 836 AN: 26422 AF XY: 0.0300

Gnomad AFR exome AF: 0.0370

Gnomad AMR exome AF: 0.0327

Gnomad ASJ exome AF: 0.0328

Gnomad EAS exome AF: 0.0289

Gnomad FIN exome AF: 0.0262

Gnomad NFE exome AF: 0.0324

Gnomad OTH exome AF: 0.0403

GnomAD4 exome AF: 0.0127 AC: 14043 AN: 1105976 Hom.: 0 AF XY: 0.0131 AC XY: 6972 AN XY: 533668

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

African (AFR) AF: 0.0176 AC: 412 AN: 23404

American (AMR) AF: 0.0313 AC: 462 AN: 14756

Ashkenazi Jewish (ASJ) AF: 0.0201 AC: 299 AN: 14900

East Asian (EAS) AF: 0.0252 AC: 670 AN: 26538

South Asian (SAS) AF: 0.0123 AC: 598 AN: 48802

European-Finnish (FIN) AF: 0.0339 AC: 798 AN: 23538

Middle Eastern (MID) AF: 0.0113 AC: 34 AN: 2998

European-Non Finnish (NFE) AF: 0.0110 AC: 9994 AN: 906584

Other (OTH) AF: 0.0175 AC: 776 AN: 44456

⚠️ 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: 82452 Hom.: 0 Cov.: 0 AF XY: 0.0000782 AC XY: 3 AN XY: 38362

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

African (AFR) AF: 0.0000500 AC: 1 AN: 20010

American (AMR) AF: 0.000137 AC: 1 AN: 7288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2384

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: 3132

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

European-Non Finnish (NFE) AF: 0.0000479 AC: 2 AN: 41780

Other (OTH) AF: 0.00 AC: 0 AN: 1128

⚠️ 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.

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;