chr5-34951045-C-A

Variant names:

• chr5-34951045-C-A
• rs37439
• NM_001012339.3:c.1358+703C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

DNAJC21 Gene-Disease associations (from GenCC):

• bone marrow failure syndrome 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Shwachman-Diamond syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012339.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC21	NM_001012339.3	MANE Select	c.1358+703C>A		intron	N/A	NP_001012339.2
	DNAJC21	NM_194283.4		c.1493+703C>A		intron	N/A	NP_919259.3
	DNAJC21	NM_001348420.2		c.1397+703C>A		intron	N/A	NP_001335349.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC21	ENST00000648817.1	MANE Select	c.1358+703C>A		intron	N/A	ENSP00000497410.1
	DNAJC21	ENST00000512136.2	TSL:2	n.2187C>A		non_coding_transcript_exon	Exon 11 of 11
	DNAJC21	ENST00000382021.2	TSL:2	c.1493+703C>A		intron	N/A	ENSP00000371451.2

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

African (AFR) AF: 0.517 AC: 8166 AN: 15786

American (AMR) AF: 0.802 AC: 789 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 3964 AN: 5152

East Asian (EAS) AF: 0.580 AC: 2106 AN: 3630

South Asian (SAS) AF: 0.666 AC: 10969 AN: 16462

European-Finnish (FIN) AF: 0.781 AC: 225 AN: 288

Middle Eastern (MID) AF: 0.764 AC: 1240 AN: 1622

European-Non Finnish (NFE) AF: 0.848 AC: 645946 AN: 761928

Other (OTH) AF: 0.796 AC: 21721 AN: 27302

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

African (AFR) AF: 0.547 AC: 22681 AN: 41492

American (AMR) AF: 0.782 AC: 11953 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2690 AN: 3466

East Asian (EAS) AF: 0.543 AC: 2801 AN: 5162

South Asian (SAS) AF: 0.666 AC: 3213 AN: 4822

European-Finnish (FIN) AF: 0.766 AC: 8118 AN: 10598

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56735 AN: 68004

Other (OTH) AF: 0.753 AC: 1591 AN: 2112

Alfa AF: 0.792 Hom.: 142894

Bravo AF: 0.725

Asia WGS AF: 0.593 AC: 2065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.086
DANN	Benign	0.79
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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: rs37439; hg19: chr5-34951150;