Genetic Variant DNAJC1:c.820+29A>G (chr10-21904493-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022365.4(DNAJC1):c.820+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 1,301,460 control chromosomes in the GnomAD database, including 328,885 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.66 ( 33391 hom., cov: 31)

Exomes 𝑓: 0.71 ( 295494 hom. )

Consequence

DNAJC1
NM_022365.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.573

Publications

11 publications found

Variant links:

Genes affected

DNAJC1 (HGNC:20090): (DnaJ heat shock protein family (Hsp40) member C1) The membrane protein encoded by this gene is a DNAJ-like heat shock protein that binds the molecular chaperone BiP. In addition, the encoded protein contains two SANT domains that have been shown to bind serpin alpha1-antichymotrypsin and inter-alpha trypsin inhibitor heavy chain 4. [provided by RefSeq, Jul 2016]

DNAJC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DNAJC1	NM_022365.4 link	c.820+29A>G	intron_variant	Intron 7 of 11	ENST00000376980.8	NP_071760.2	Q96KC8
DNAJC1	XM_011519614.4 link	c.820+29A>G	intron_variant	Intron 7 of 9		XP_011517916.1
DNAJC1	XM_017016536.3 link	c.820+29A>G	intron_variant	Intron 7 of 8		XP_016872025.1
DNAJC1	XM_047425628.1 link	c.820+29A>G	intron_variant	Intron 7 of 9		XP_047281584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC1	ENST00000376980.8 link	c.820+29A>G		intron_variant	Intron 7 of 11	1	NM_022365.4	ENSP00000366179.3		Q96KC8

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

99540

AN:

151748

Hom.:

33380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.543

Gnomad AMI

AF:

0.536

Gnomad AMR

AF:

0.645

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.984

Gnomad SAS

AF:

0.798

Gnomad FIN

AF:

0.701

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.695

Gnomad OTH

AF:

0.631

GnomAD2 exomes

AF:

0.712

AC:

134007

AN:

188232

AF XY:

0.716

show subpopulations

Gnomad AFR exome

AF:

0.547

Gnomad AMR exome

AF:

0.702

Gnomad ASJ exome

AF:

0.541

Gnomad EAS exome

AF:

0.988

Gnomad FIN exome

AF:

0.711

Gnomad NFE exome

AF:

0.692

Gnomad OTH exome

AF:

0.686

GnomAD4 exome

AF:

0.713

AC:

819316

AN:

1149594

Hom.:

295494

Cov.:

AF XY:

0.714

AC XY:

413864

AN XY:

579430

show subpopulations

African (AFR)

AF:

0.537

AC:

13264

AN:

24720

American (AMR)

AF:

0.681

AC:

18891

AN:

27742

Ashkenazi Jewish (ASJ)

AF:

0.532

AC:

11291

AN:

21236

East Asian (EAS)

AF:

0.990

AC:

35511

AN:

35868

South Asian (SAS)

AF:

0.790

AC:

49373

AN:

62484

European-Finnish (FIN)

AF:

0.716

AC:

35857

AN:

50086

Middle Eastern (MID)

AF:

0.558

AC:

2687

AN:

4816

European-Non Finnish (NFE)

AF:

0.708

AC:

618719

AN:

874070

Other (OTH)

AF:

0.694

AC:

33723

AN:

48572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

10768

21536

32305

43073

53841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14950

29900

44850

59800

74750

<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:

0.656

AC:

99578

AN:

151866

Hom.:

33391

Cov.:

AF XY:

0.660

AC XY:

48978

AN XY:

74198

show subpopulations

African (AFR)

AF:

0.542

AC:

22464

AN:

41434

American (AMR)

AF:

0.645

AC:

9848

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

1821

AN:

3472

East Asian (EAS)

AF:

0.984

AC:

5106

AN:

5188

South Asian (SAS)

AF:

0.797

AC:

3838

AN:

4814

European-Finnish (FIN)

AF:

0.701

AC:

7344

AN:

10470

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.695

AC:

47188

AN:

67904

Other (OTH)

AF:

0.633

AC:

1333

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1701

3402

5104

6805

8506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<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:

0.675

Hom.:

21996

Bravo

AF:

0.644

Asia WGS

AF:

0.839

AC:

2896

AN:

3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.012

(source)

DANN

Benign

0.72

PhyloP100

-0.57

Mutation Taster

=100/0

polymorphism (auto)

(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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over