rs37439

Positions:

• chr5-34951045-C-A
• chr5-34951045-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012339.3(DNAJC21):​c.1358+703C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 985,298 control chromosomes in the GnomAD database, including 332,913 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.73 (41588 hom., cov: 33)
  • Exomes 𝑓: 0.83 (291325 hom.)
• Consequence: DNAJC21 NM_001012339.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC21	NM_001012339.3	c.1358+703C>A		intron_variant		ENST00000648817.1	NP_001012339.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC21	ENST00000648817.1	c.1358+703C>A		intron_variant			NM_001012339.3	ENSP00000497410	P1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110681 AN: 152026 Hom.: 41567 Cov.: 33

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.756

GnomAD4 exome AF: 0.834 AC: 695126 AN: 833154 Hom.: 291325 Cov.: 62 AF XY: 0.833 AC XY: 320603 AN XY: 384742

Gnomad4 AFR exome AF: 0.517

Gnomad4 AMR exome AF: 0.802

Gnomad4 ASJ exome AF: 0.769

Gnomad4 EAS exome AF: 0.580

Gnomad4 SAS exome AF: 0.666

Gnomad4 FIN exome AF: 0.781

Gnomad4 NFE exome AF: 0.848

Gnomad4 OTH exome AF: 0.796

GnomAD4 genome AF: 0.728 AC: 110735 AN: 152144 Hom.: 41588 Cov.: 33 AF XY: 0.724 AC XY: 53831 AN XY: 74394

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.834

Gnomad4 OTH AF: 0.753

Alfa AF: 0.813 Hom.: 86879

Bravo AF: 0.725

Asia WGS AF: 0.593 AC: 2065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.086
DANN	Benign	0.79

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: rs37439; hg19: chr5-34951150;