rs772171513

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-34929851-G-C
• chr5-34929851-G-T
• chr5-34929851-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001012339.3(DNAJC21):​c.32G>C​(p.Arg11Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,425,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R11L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: DNAJC21 NM_001012339.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.724
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16318887).

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.32G>C	p.Arg11Pro	missense	Exon 1 of 12	NP_001012339.2	Q5F1R6-1
	DNAJC21	NM_194283.4		c.32G>C	p.Arg11Pro	missense	Exon 1 of 13	NP_919259.3	Q5F1R6-2
	DNAJC21	NM_001348420.2		c.32G>C	p.Arg11Pro	missense	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.32G>C	p.Arg11Pro	missense	Exon 1 of 12	ENSP00000497410.1	Q5F1R6-1
	DNAJC21	ENST00000966889.1		c.32G>C	p.Arg11Pro	missense	Exon 1 of 14	ENSP00000636948.1
	DNAJC21	ENST00000382021.2	TSL:2	c.32G>C	p.Arg11Pro	missense	Exon 1 of 13	ENSP00000371451.2	Q5F1R6-2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00000464 AC: 1 AN: 215552 AF XY: 0.00000843

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000103

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1425856 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 709372

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30100

American (AMR) AF: 0.00 AC: 0 AN: 41644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25042

East Asian (EAS) AF: 0.00 AC: 0 AN: 35318

South Asian (SAS) AF: 0.00 AC: 0 AN: 83046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5402

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1094884

Other (OTH) AF: 0.00 AC: 0 AN: 58598

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000827 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.70	N
PhyloP100		0.72
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.068
Sift	Benign	0.42	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.47		Loss of MoRF binding (P = 0.0521)
MVP		0.29
MPC		0.083
ClinPred		0.16	T
GERP RS		1.1
PromoterAI		-0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.27
gMVP		0.54
Mutation Taster		=74/26	polymorphism

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: rs772171513; hg19: chr5-34929956;