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GeneBe

5-34929870-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001012339.3(DNAJC21):c.51G>A(p.Glu17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,583,812 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 0.00013 ( 0 hom., cov: 29)
Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

DNAJC21
NM_001012339.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.578
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-34929870-G-A is Benign according to our data. Variant chr5-34929870-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 717195.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.578 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNAJC21NM_001012339.3 linkuse as main transcriptc.51G>A p.Glu17= synonymous_variant 1/12 ENST00000648817.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNAJC21ENST00000648817.1 linkuse as main transcriptc.51G>A p.Glu17= synonymous_variant 1/12 NM_001012339.3 P1Q5F1R6-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000125
AC:
19
AN:
151666
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0000725
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:
0.000236
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000999
AC:
22
AN:
220156
Hom.:
0
AF XY:
0.000108
AC XY:
13
AN XY:
120782
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000322
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000107
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000171
Gnomad OTH exome
AF:
0.000194
GnomAD4 exome
AF:
0.000146
AC:
209
AN:
1432146
Hom.:
0
Cov.:
31
AF XY:
0.000143
AC XY:
102
AN XY:
712450
show subpopulations
Gnomad4 AFR exome
AF:
0.0000987
Gnomad4 AMR exome
AF:
0.0000237
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000958
Gnomad4 FIN exome
AF:
0.0000192
Gnomad4 NFE exome
AF:
0.000168
Gnomad4 OTH exome
AF:
0.000186
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000125
AC:
19
AN:
151666
Hom.:
0
Cov.:
29
AF XY:
0.0000810
AC XY:
6
AN XY:
74060
show subpopulations
Gnomad4 AFR
AF:
0.0000725
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000236
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000186
Hom.:
0
Bravo
AF:
0.000128

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 09, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
Cadd
Benign
14
Dann
Benign
0.95
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs769606764; hg19: chr5-34929975; COSMIC: COSV57762069; COSMIC: COSV57762069; API