Genetic Variant DNAJC28:p.Ile267Val (chr21-33488595-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040192.3(DNAJC28):c.799A>G(p.Ile267Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

DNAJC28
NM_001040192.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86

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: 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=0.11489469).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC28	NM_001040192.3 link	c.799A>G	p.Ile267Val	missense_variant	Exon 2 of 2	ENST00000381947.4	NP_001035282.1	Q9NX36
DNAJC28	NM_001320746.3 link	c.799A>G	p.Ile267Val	missense_variant	Exon 2 of 2		NP_001307675.1	Q9NX36
DNAJC28	NM_017833.5 link	c.799A>G	p.Ile267Val	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.799A>G	p.Ile267Val	missense_variant	Exon 2 of 2	1	NM_001040192.3	ENSP00000371373.3	Q9NX36
DNAJC28	ENST00000314399.3 link	c.799A>G	p.Ile267Val	missense_variant	Exon 2 of 2	1		ENSP00000320303.3	Q9NX36
DNAJC28	ENST00000402202.1 link	c.799A>G	p.Ile267Val	missense_variant	Exon 2 of 2	5		ENSP00000385777.1	Q9NX36

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251164

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

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:

0.00000479

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.0000895

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111974

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.799A>G (p.I267V) alteration is located in exon 2 (coding exon 1) of the DNAJC28 gene. This alteration results from a A to G substitution at nucleotide position 799, causing the isoleucine (I) at amino acid position 267 to be replaced by a valine (V). 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

0.070

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0032

T;T;T;T

Eigen

Benign

-0.092

Eigen_PC

Benign

-0.071

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.0051

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.9

L;L;L;L

PhyloP100

2.9

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.24

.;N;N;N

REVEL

Benign

0.089

Sift

Benign

0.061

.;T;T;T

Sift4G

Benign

0.37

T;T;T;T

Polyphen

0.63

P;P;P;P

Vest4

0.15

MutPred

0.55

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MVP

0.30

MPC

0.11

ClinPred

0.28

GERP RS

3.0

Varity_R

0.034

gMVP

0.40

Mutation Taster

=91/9

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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21-33488595-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over