rs150576702

Positions:

• chr5-34937404-C-G
• chr5-34937404-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001012339.3(DNAJC21):​c.517C>G​(p.Arg173Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,858 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DNAJC21 NM_001012339.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.69

Genes affected

DNAJC21 (HGNC:27030): (DnaJ heat shock protein family (Hsp40) member C21) This gene encodes a member of the DNAJ heat shock protein 40 family of proteins that is characterized by two N-terminal tetratricopeptide repeat domains and a C-terminal DNAJ domain. This protein binds the precursor 45S ribosomal RNA and may be involved in early nuclear ribosomal RNA biogenesis and maturation of the 60S ribosomal subunit. Mutations in this gene result in Bone marrow failure syndrome 3. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC21	NM_001012339.3	c.517C>G	p.Arg173Gly	missense_variant	5/12	ENST00000648817.1	NP_001012339.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC21	ENST00000648817.1	c.517C>G	p.Arg173Gly	missense_variant	5/12		NM_001012339.3	ENSP00000497410	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T;.;.;.;.;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	.;D;D;D;D;D;D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.69	D;D;D;D;D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.8	M;M;M;M;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.1	.;D;D;.;.;.;.
REVEL	Uncertain	0.33
Sift	Uncertain	0.0080	.;D;D;.;.;.;.
Sift4G	Uncertain	0.016	.;D;D;.;.;.;.
Polyphen		0.88	P;P;D;D;.;.;.
Vest4		0.90, 0.88
MutPred		0.35		Loss of MoRF binding (P = 0.028);Loss of MoRF binding (P = 0.028);Loss of MoRF binding (P = 0.028);Loss of MoRF binding (P = 0.028);.;.;.;
MVP		0.82
MPC		0.31
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.62
gMVP		0.49

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: rs150576702; hg19: chr5-34937509;