rs12137794

chr1-6645884-C-T

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC11	NM_018198.4	c.799G>A	p.Val267Met	missense_variant	8/16	ENST00000377577.10
DNAJC11	XM_047424842.1	c.529G>A	p.Val177Met	missense_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC11	ENST00000377577.10	c.799G>A	p.Val267Met	missense_variant	8/16	1	NM_018198.4	P1

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

GnomAD3 exomes AF: 0.0732 AC: 18409 AN: 251482 Hom.: 846 AF XY: 0.0729 AC XY: 9913 AN XY: 135918

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 SAS exome AF: 0.0498

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

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.0672

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0524

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.0861

Gnomad4 OTH exome AF: 0.0680

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

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.0969

Gnomad4 ASJ AF: 0.0602

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0492

Gnomad4 FIN AF: 0.0993

Gnomad4 NFE AF: 0.0866

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0776 Hom.: 1266

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 v4.3

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
Eigen	Benign	-0.18
Eigen_PC	Benign	0.054
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.88	D;D;D;D
MetaRNN	Benign	0.0021	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.28	N;N;N;N
REVEL	Benign	0.093
Sift	Benign	0.27	T;T;T;T
Sift4G	Benign	0.38	T;T;T;.
Polyphen		0.22	B;B;B;.
Vest4		0.097, 0.058
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

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

Publications

LitVar

Other links and lift over

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