Genetic Variant DNAJC28:p.Ser89Cys (chr21-33489128-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001040192.3(DNAJC28):c.266C>G(p.Ser89Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 in 1,613,752 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

DNAJC28
NM_001040192.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.16

Publications

1 publications found

Variant links:

Genes affected

DNAJC28 (HGNC:1297): (DnaJ heat shock protein family (Hsp40) member C28) This gene encodes a member of the DnaJ heat shock protein family. The encoded protein, which contains a conserved N-terminal DnaJ domain, is thought to play a role in protein folding or act as a molecular chaperone protein. [provided by RefSeq, Oct 2016]

DNAJC28 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16858956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC28	NM_001040192.3 link	c.266C>G	p.Ser89Cys	missense_variant	Exon 2 of 2	ENST00000381947.4	NP_001035282.1	Q9NX36
DNAJC28	NM_001320746.3 link	c.266C>G	p.Ser89Cys	missense_variant	Exon 2 of 2		NP_001307675.1	Q9NX36
DNAJC28	NM_017833.5 link	c.266C>G	p.Ser89Cys	missense_variant	Exon 2 of 2		NP_060303.2	Q9NX36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAJC28	ENST00000381947.4 link	c.266C>G	p.Ser89Cys	missense_variant	Exon 2 of 2	1	NM_001040192.3	ENSP00000371373.3	Q9NX36
DNAJC28	ENST00000314399.3 link	c.266C>G	p.Ser89Cys	missense_variant	Exon 2 of 2	1		ENSP00000320303.3	Q9NX36
DNAJC28	ENST00000402202.1 link	c.266C>G	p.Ser89Cys	missense_variant	Exon 2 of 2	5		ENSP00000385777.1	Q9NX36

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.0000876

AC:

AN:

251080

AF XY:

0.0000884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461600

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.0000448

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.000580

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111964

Other (OTH)

AF:

0.000149

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41430

American (AMR)

AF:

0.0000656

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.000955

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 19, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.266C>G (p.S89C) alteration is located in exon 2 (coding exon 1) of the DNAJC28 gene. This alteration results from a C to G substitution at nucleotide position 266, causing the serine (S) at amino acid position 89 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T;T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.014

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Uncertain

0.19

MutationAssessor

Benign

1.7

L;L;L;L

PhyloP100

6.2

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.1

.;N;N;N

REVEL

Uncertain

0.41

Sift

Benign

0.040

.;D;D;D

Sift4G

Uncertain

0.027

D;D;D;D

Polyphen

0.99

D;D;D;D

Vest4

0.27

MutPred

0.71

Loss of disorder (P = 0.0252);Loss of disorder (P = 0.0252);Loss of disorder (P = 0.0252);Loss of disorder (P = 0.0252);

MVP

0.76

MPC

0.23

ClinPred

0.15

GERP RS

5.8

Varity_R

0.17

gMVP

0.26

Mutation Taster

=57/43

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

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

21-33489128-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over