Genetic Variant NM_017626.7:c.*30+485C>T (chr10-72335295-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_017626.7(DNAJB12):c.*30+485C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 987,580 control chromosomes in the GnomAD database, including 3,564 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 0.12 ( 2347 hom., cov: 33)

Exomes 𝑓: 0.034 ( 1217 hom. )

Consequence

DNAJB12
NM_017626.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.64

Publications

1 publications found

Variant links:

Genes affected

DNAJB12 (HGNC:14891): (DnaJ heat shock protein family (Hsp40) member B12) DNAJB12 belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJ proteins may have up to 3 distinct domains: a conserved 70-amino acid J domain, usually at the N terminus; a glycine/phenylalanine (G/F)-rich region; and a cysteine-rich domain containing 4 motifs resembling a zinc finger domain (Ohtsuka and Hata, 2000 [PubMed 11147971]).[supplied by OMIM, Mar 2008]

DNAJB12 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB12	NM_017626.7 link	c.*30+485C>T		intron_variant	Intron 8 of 8	ENST00000444643.8	NP_060096.4	Q9NXW2-1J3KPS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB12	ENST00000444643.8 link	c.*30+485C>T		intron_variant	Intron 8 of 8	1	NM_017626.7	ENSP00000403313.2		Q9NXW2-1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17704

AN:

152128

Hom.:

2325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0593

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.0683

Gnomad FIN

AF:

0.0213

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0282

Gnomad OTH

AF:

0.0961

GnomAD4 exome

AF:

0.0344

AC:

28769

AN:

835334

Hom.:

1217

Cov.:

AF XY:

0.0337

AC XY:

13020

AN XY:

385992

show subpopulations

African (AFR)

AF:

0.329

AC:

5199

AN:

15804

American (AMR)

AF:

0.0492

AC:

AN:

1178

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

120

AN:

5186

East Asian (EAS)

AF:

0.130

AC:

473

AN:

3652

South Asian (SAS)

AF:

0.0608

AC:

1029

AN:

16936

European-Finnish (FIN)

AF:

0.0206

AC:

AN:

436

Middle Eastern (MID)

AF:

0.0623

AC:

101

AN:

1620

European-Non Finnish (NFE)

AF:

0.0267

AC:

20341

AN:

763150

Other (OTH)

AF:

0.0526

AC:

1439

AN:

27372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1779

3557

5336

7114

8893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1202

2404

3606

4808

6010

<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:

0.117

AC:

17768

AN:

152246

Hom.:

2347

Cov.:

AF XY:

0.114

AC XY:

8508

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.323

AC:

13409

AN:

41522

American (AMR)

AF:

0.0592

AC:

905

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0271

AC:

AN:

3472

East Asian (EAS)

AF:

0.121

AC:

625

AN:

5172

South Asian (SAS)

AF:

0.0677

AC:

327

AN:

4828

European-Finnish (FIN)

AF:

0.0213

AC:

226

AN:

10616

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0282

AC:

1919

AN:

68016

Other (OTH)

AF:

0.0956

AC:

202

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

689

1378

2066

2755

3444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.0782

Hom.:

175

Bravo

AF:

0.130

Asia WGS

AF:

0.121

AC:

419

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.60

(source)

DANN

Benign

0.61

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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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