chr5-34929851-G-A

Variant names:

• chr5-34929851-G-A
• rs772171513
• NM_001012339.3:c.32G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001012339.3(DNAJC21):​c.32G>A​(p.Arg11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,425,856 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAJC21 NM_001012339.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.724

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]

LOC124900961 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1497631).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC21	NM_001012339.3	c.32G>A	p.Arg11Gln	missense_variant	Exon 1 of 12	ENST00000648817.1	NP_001012339.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC21	ENST00000648817.1	c.32G>A	p.Arg11Gln	missense_variant	Exon 1 of 12		NM_001012339.3	ENSP00000497410.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD3 exomes AF: 0.00000464 AC: 1 AN: 215552 Hom.: 0 AF XY: 0.00000843 AC XY: 1 AN XY: 118650

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000103

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1425856 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 709372

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000283

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.13e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T;T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.90	.;D;D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.72	N;N;N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.81	.;N;N;.
REVEL	Benign	0.053
Sift	Benign	0.63	.;T;T;.
Sift4G	Benign	0.59	.;T;T;.
Polyphen		0.012	B;B;B;.
Vest4		0.12, 0.14
MutPred		0.40		Loss of MoRF binding (P = 0.0716);Loss of MoRF binding (P = 0.0716);Loss of MoRF binding (P = 0.0716);Loss of MoRF binding (P = 0.0716);
MVP		0.44
MPC		0.070
ClinPred		0.18	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.18

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: rs772171513; hg19: chr5-34929956;