rs12137794

Variant names:

• chr1-6645884-C-T
• rs12137794
• NM_018198.4:c.799G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018198.4(DNAJC11):​c.799G>A​(p.Val267Met) variant causes a missense change. The variant allele was found at a frequency of 0.0787 in 1,614,104 control chromosomes in the GnomAD database, including 5,510 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.064 (424 hom., cov: 32)
  • Exomes 𝑓: 0.080 (5086 hom.)
• Consequence: DNAJC11 NM_018198.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.66
• Publications: 25 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021018386).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0928 is higher than 0.05.

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.799G>A	p.Val267Met	missense	Exon 8 of 16	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.799G>A	p.Val267Met	missense	Exon 8 of 16	ENSP00000366800.5	Q9NVH1-1
	DNAJC11	ENST00000294401.11	TSL:1	c.799G>A	p.Val267Met	missense	Exon 8 of 15	ENSP00000294401.7	Q9NVH1-3
	DNAJC11	ENST00000451196.5	TSL:1	c.727G>A	p.Val243Met	missense	Exon 7 of 8	ENSP00000415871.1	Q5TH61

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9669 AN: 152120 Hom.: 423 Cov.: 32

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0967

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0483

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.0664

GnomAD2 exomes AF: 0.0732 AC: 18409 AN: 251482 AF XY: 0.0729

Gnomad AFR exome AF: 0.0125

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.0632

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.102

Gnomad NFE exome AF: 0.0838

Gnomad OTH exome AF: 0.0725

GnomAD4 exome AF: 0.0803 AC: 117327 AN: 1461866 Hom.: 5086 Cov.: 33 AF XY: 0.0797 AC XY: 57969 AN XY: 727234

African (AFR) AF: 0.0125 AC: 419 AN: 33480

American (AMR) AF: 0.115 AC: 5130 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0672 AC: 1757 AN: 26134

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39700

South Asian (SAS) AF: 0.0524 AC: 4518 AN: 86258

European-Finnish (FIN) AF: 0.102 AC: 5454 AN: 53418

Middle Eastern (MID) AF: 0.0388 AC: 224 AN: 5768

European-Non Finnish (NFE) AF: 0.0861 AC: 95712 AN: 1111994

Other (OTH) AF: 0.0680 AC: 4104 AN: 60392

GnomAD4 genome AF: 0.0636 AC: 9677 AN: 152238 Hom.: 424 Cov.: 32 AF XY: 0.0643 AC XY: 4786 AN XY: 74446

African (AFR) AF: 0.0153 AC: 636 AN: 41550

American (AMR) AF: 0.0969 AC: 1481 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0492 AC: 237 AN: 4820

European-Finnish (FIN) AF: 0.0993 AC: 1053 AN: 10604

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0866 AC: 5889 AN: 68006

Other (OTH) AF: 0.0653 AC: 138 AN: 2114

Alfa AF: 0.0751 Hom.: 1637

Bravo AF: 0.0590

TwinsUK AF: 0.0885 AC: 328

ALSPAC AF: 0.0869 AC: 335

ESP6500AA AF: 0.0170 AC: 75

ESP6500EA AF: 0.0823 AC: 708

ExAC AF: 0.0692 AC: 8406

Asia WGS AF: 0.0210 AC: 75 AN: 3478

EpiCase AF: 0.0748

EpiControl AF: 0.0759

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Benign	0.88
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.054
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N
PhyloP100		5.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.093
Sift	Benign	0.27	T
Sift4G	Benign	0.38	T
Polyphen		0.22	B
Vest4		0.097
MPC		0.48
ClinPred		0.019	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.053
gMVP		0.21
Mutation Taster		=98/2	polymorphism (auto)

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: rs12137794; hg19: chr1-6705944; COSMIC: COSV53791469; COSMIC: COSV53791469;