dbSNP rs1266840568: DNAJC21:c.-171delC (chr5-34929647-AC-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001012339.3(DNAJC21):c.-171delC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000689 in 145,148 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAJC21
NM_001012339.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

Publications

0 publications found

Variant links:

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

DNAJC21 links:

LOC124900961 (HGNC:):

LOC124900961 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC21	NM_001012339.3 link	c.-171delC		5_prime_UTR_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 link	c.-171delC		5_prime_UTR_variant	Exon 1 of 12		NM_001012339.3	ENSP00000497410.1		Q5F1R6-1

Frequencies

GnomAD3 genomes

AF:

0.00000689

AC:

AN:

145148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

14062

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

8870

African (AFR)

AF:

0.00

AC:

AN:

178

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

108

East Asian (EAS)

AF:

0.00

AC:

AN:

330

South Asian (SAS)

AF:

0.00

AC:

AN:

1044

European-Finnish (FIN)

AF:

0.00

AC:

AN:

180

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

11666

Other (OTH)

AF:

0.00

AC:

AN:

440

GnomAD4 genome

AF:

0.00000689

AC:

AN:

145148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70564

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39946

American (AMR)

AF:

0.00

AC:

AN:

14734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3402

East Asian (EAS)

AF:

0.00

AC:

AN:

4784

South Asian (SAS)

AF:

0.00

AC:

AN:

4466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.0000152

AC:

AN:

65680

Other (OTH)

AF:

0.00

AC:

AN:

2014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DNAJC21: PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=295/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over