NM_001012339.3:c.21G>T

Variant names:

• chr5-34929840-G-T
• rs754143117
• NM_001012339.3:c.21G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001012339.3(DNAJC21):​c.21G>T​(p.Ala7Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000699 in 1,572,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: DNAJC21 NM_001012339.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13
• Publications: 0 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: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• Shwachman-Diamond syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124900961 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 5-34929840-G-T is Benign according to our data. Variant chr5-34929840-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2891321.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.13 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC21	NM_001012339.3	MANE Select	c.21G>T	p.Ala7Ala	synonymous	Exon 1 of 12	NP_001012339.2	Q5F1R6-1
	DNAJC21	NM_194283.4		c.21G>T	p.Ala7Ala	synonymous	Exon 1 of 13	NP_919259.3	Q5F1R6-2
	DNAJC21	NM_001348420.2		c.21G>T	p.Ala7Ala	synonymous	Exon 1 of 12	NP_001335349.1	Q5F1R6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC21	ENST00000648817.1	MANE Select	c.21G>T	p.Ala7Ala	synonymous	Exon 1 of 12	ENSP00000497410.1	Q5F1R6-1
	DNAJC21	ENST00000966889.1		c.21G>T	p.Ala7Ala	synonymous	Exon 1 of 14	ENSP00000636948.1
	DNAJC21	ENST00000382021.2	TSL:2	c.21G>T	p.Ala7Ala	synonymous	Exon 1 of 13	ENSP00000371451.2	Q5F1R6-2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 150952 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000187 AC: 4 AN: 213418 AF XY: 0.00000849

Gnomad AFR exome AF: 0.000351

Gnomad AMR exome AF: 0.00

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: 0.00000633 AC: 9 AN: 1421736 Hom.: 0 Cov.: 31 AF XY: 0.00000707 AC XY: 5 AN XY: 707352

African (AFR) AF: 0.000100 AC: 3 AN: 29924

American (AMR) AF: 0.00 AC: 0 AN: 41442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24858

East Asian (EAS) AF: 0.00 AC: 0 AN: 34996

South Asian (SAS) AF: 0.00 AC: 0 AN: 82798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5252

European-Non Finnish (NFE) AF: 0.00000549 AC: 6 AN: 1092638

Other (OTH) AF: 0.00 AC: 0 AN: 58320

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 150952 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 73688

African (AFR) AF: 0.0000242 AC: 1 AN: 41262

American (AMR) AF: 0.00 AC: 0 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67616

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.95
PhyloP100		-1.1
PromoterAI		-0.075	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs754143117; hg19: chr5-34929945;