dbSNP rs200459314: DNAJC21:c.97+5G>A (chr5-34929921-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001012339.3(DNAJC21):c.97+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000543 in 1,570,026 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00057 ( 14 hom. )

Consequence

DNAJC21
NM_001012339.3 splice_region, intron

Scores

Splicing: ADA: 0.9907

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.702

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: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 5-34929921-G-A is Benign according to our data. Variant chr5-34929921-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 724583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000289 (44/152102) while in subpopulation SAS AF = 0.00911 (44/4830). AF 95% confidence interval is 0.00697. There are 0 homozygotes in GnomAd4. There are 35 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAJC21	NM_001012339.3	MANE Select	c.97+5G>A	splice_region intron	N/A	NP_001012339.2	Q5F1R6-1
DNAJC21	NM_194283.4		c.97+5G>A	splice_region intron	N/A	NP_919259.3	Q5F1R6-2
DNAJC21	NM_001348420.2		c.97+5G>A	splice_region intron	N/A	NP_001335349.1	Q5F1R6-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAJC21	ENST00000648817.1	MANE Select	c.97+5G>A	splice_region intron	N/A	ENSP00000497410.1	Q5F1R6-1
DNAJC21	ENST00000966889.1		c.97+5G>A	splice_region intron	N/A	ENSP00000636948.1
DNAJC21	ENST00000382021.2	TSL:2	c.97+5G>A	splice_region intron	N/A	ENSP00000371451.2	Q5F1R6-2

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

151986

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:

0.00910

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00125

AC:

261

AN:

209028

AF XY:

0.00173

show subpopulations

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000571

AC:

809

AN:

1417924

Hom.:

Cov.:

AF XY:

0.000848

AC XY:

598

AN XY:

704922

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30058

American (AMR)

AF:

0.00

AC:

AN:

41006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24858

East Asian (EAS)

AF:

0.00

AC:

AN:

35198

South Asian (SAS)

AF:

0.00947

AC:

777

AN:

82048

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5552

European-Non Finnish (NFE)

AF:

9.18e-7

AC:

AN:

1089662

Other (OTH)

AF:

0.000533

AC:

AN:

58180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

109

145

181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000289

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41520

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00911

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67950

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000693

Hom.:

Bravo

AF:

0.0000491

Asia WGS

AF:

0.00404

AC:

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

0.70

PromoterAI

-0.37

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Benign

0.68

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over