Genetic Variant DNAJC17:c.*751A>G (chr15-40767189-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_018163.3(DNAJC17):c.*751A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0434 in 1,457,468 control chromosomes in the GnomAD database, including 1,869 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 0.069 ( 526 hom., cov: 33)

Exomes 𝑓: 0.040 ( 1343 hom. )

Consequence

DNAJC17
NM_018163.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.208

Publications

5 publications found

Variant links:

Genes affected

DNAJC17 (HGNC:25556): (DnaJ heat shock protein family (Hsp40) member C17) Predicted to enable RNA binding activity. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II and toxin transport. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC17 links:

GCHFR (HGNC:4194): (GTP cyclohydrolase I feedback regulator) GTP cyclohydrolase I feedback regulatory protein binds to and mediates tetrahydrobiopterin inhibition of GTP cyclohydrolase I. The regulatory protein, GCHFR, consists of a homodimer. It is postulated that GCHFR may play a role in regulating phenylalanine metabolism in the liver and in the production of biogenic amine neurotransmitters and nitric oxide. [provided by RefSeq, Jul 2008]

GCHFR links:

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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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC17	NM_018163.3 link	c.*751A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000220496.9	NP_060633.1
GCHFR	NM_005258.3 link	c.132-37T>C		intron_variant	Intron 2 of 2	ENST00000260447.6	NP_005249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC17	ENST00000220496.9 link	c.*751A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_018163.3	ENSP00000220496.4
GCHFR	ENST00000260447.6 link	c.132-37T>C		intron_variant	Intron 2 of 2	1	NM_005258.3	ENSP00000260447.4

Frequencies

GnomAD3 genomes

AF:

0.0686

AC:

10388

AN:

151534

Hom.:

524

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.0566

Gnomad ASJ

AF:

0.0669

Gnomad EAS

AF:

0.0260

Gnomad SAS

AF:

0.0739

Gnomad FIN

AF:

0.0220

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0376

Gnomad OTH

AF:

0.0737

GnomAD2 exomes

AF:

0.0456

AC:

6562

AN:

143918

AF XY:

0.0443

show subpopulations

Gnomad AFR exome

AF:

0.135

Gnomad AMR exome

AF:

0.0298

Gnomad ASJ exome

AF:

0.0563

Gnomad EAS exome

AF:

0.0215

Gnomad FIN exome

AF:

0.0235

Gnomad NFE exome

AF:

0.0396

Gnomad OTH exome

AF:

0.0473

GnomAD4 exome

AF:

0.0405

AC:

52863

AN:

1305818

Hom.:

1343

Cov.:

AF XY:

0.0408

AC XY:

25964

AN XY:

637010

show subpopulations

African (AFR)

AF:

0.136

AC:

3642

AN:

26726

American (AMR)

AF:

0.0369

AC:

875

AN:

23738

Ashkenazi Jewish (ASJ)

AF:

0.0628

AC:

1227

AN:

19544

East Asian (EAS)

AF:

0.0286

AC:

918

AN:

32072

South Asian (SAS)

AF:

0.0611

AC:

3754

AN:

61490

European-Finnish (FIN)

AF:

0.0247

AC:

1218

AN:

49330

Middle Eastern (MID)

AF:

0.0908

AC:

475

AN:

5234

European-Non Finnish (NFE)

AF:

0.0369

AC:

38169

AN:

1034030

Other (OTH)

AF:

0.0482

AC:

2585

AN:

53654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

2195

4390

6586

8781

10976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1572

3144

4716

6288

7860

<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:

0.0686

AC:

10406

AN:

151650

Hom.:

526

Cov.:

AF XY:

0.0668

AC XY:

4954

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.140

AC:

5737

AN:

40952

American (AMR)

AF:

0.0564

AC:

862

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0669

AC:

232

AN:

3468

East Asian (EAS)

AF:

0.0261

AC:

135

AN:

5174

South Asian (SAS)

AF:

0.0731

AC:

353

AN:

4828

European-Finnish (FIN)

AF:

0.0220

AC:

233

AN:

10610

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0376

AC:

2555

AN:

68008

Other (OTH)

AF:

0.0729

AC:

154

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

486

972

1459

1945

2431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0596

Hom.:

135

Bravo

AF:

0.0731

Asia WGS

AF:

0.0580

AC:

203

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.2

(source)

DANN

Benign

0.70

PhyloP100

-0.21

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

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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