NM_018198.4:c.1511C>G

Variant names:

• chr1-6637211-G-C
• rs774995067
• NM_018198.4:c.1511C>G

Variant summary

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

The NM_018198.4(DNAJC11):​c.1511C>G​(p.Thr504Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T504M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DNAJC11 NM_018198.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.36
• Publications: 1 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: Very rare variant in population databases, with high coverage

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.1511C>G	p.Thr504Arg	missense	Exon 14 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.1511C>G	p.Thr504Arg	missense	Exon 14 of 16	ENSP00000366800.5	Q9NVH1-1
	DNAJC11	ENST00000294401.11	TSL:1	c.1355C>G	p.Thr452Arg	missense	Exon 13 of 15	ENSP00000294401.7	Q9NVH1-3
	DNAJC11	ENST00000451196.5	TSL:1	c.741-2427C>G		intron	N/A	ENSP00000415871.1	Q5TH61

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251446 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		9.4
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.11
Sift	Benign	0.35	T
Sift4G	Benign	0.37	T
Polyphen		0.68	P
Vest4		0.82
MutPred		0.42		Loss of ubiquitination at K508 (P = 0.0418)
MVP		0.17
MPC		1.3
ClinPred		0.82	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.41
gMVP		0.74
Mutation Taster		=12/88	disease causing

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: rs774995067; hg19: chr1-6697271;