Genetic Variant NM_015291.4:c.1600A>C (chr1-15565920-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_015291.4(DNAJC16):c.1600A>C(p.Arg534Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,612,318 control chromosomes in the GnomAD database, including 58,765 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 10668 hom., cov: 30)

Exomes 𝑓: 0.25 ( 48097 hom. )

Consequence

DNAJC16
NM_015291.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0007144

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.48

Publications

19 publications found

Variant links:

Genes affected

DNAJC16 (HGNC:29157): (DnaJ heat shock protein family (Hsp40) member C16) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC16 links:

ENSG00000272510 (HGNC:):

ENSG00000272510 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP7

Synonymous conserved (PhyloP=1.48 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015291.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAJC16	NM_015291.4	MANE Select	c.1600A>C	p.Arg534Arg	splice_region synonymous	Exon 12 of 15	NP_056106.1
DNAJC16	NM_001287811.2		c.664A>C	p.Arg222Arg	splice_region synonymous	Exon 11 of 14	NP_001274740.1
DNAJC16	NR_109898.2		n.1729A>C		splice_region non_coding_transcript_exon	Exon 12 of 15

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAJC16	ENST00000375847.8	TSL:1 MANE Select	c.1600A>C	p.Arg534Arg	splice_region synonymous	Exon 12 of 15	ENSP00000365007.3
DNAJC16	ENST00000375849.5	TSL:1	c.1600A>C	p.Arg534Arg	splice_region synonymous	Exon 12 of 15	ENSP00000365009.1
DNAJC16	ENST00000616884.4	TSL:1	c.664A>C	p.Arg222Arg	splice_region synonymous	Exon 11 of 14	ENSP00000480224.1

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51199

AN:

151548

Hom.:

10632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.584

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.0648

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.312

GnomAD2 exomes

AF:

0.246

AC:

61871

AN:

251038

AF XY:

0.244

show subpopulations

Gnomad AFR exome

AF:

0.576

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.276

Gnomad EAS exome

AF:

0.0655

Gnomad FIN exome

AF:

0.299

Gnomad NFE exome

AF:

0.253

Gnomad OTH exome

AF:

0.255

GnomAD4 exome

AF:

0.248

AC:

361884

AN:

1460652

Hom.:

48097

Cov.:

AF XY:

0.247

AC XY:

179223

AN XY:

726752

show subpopulations

African (AFR)

AF:

0.589

AC:

19678

AN:

33412

American (AMR)

AF:

0.152

AC:

6775

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

7303

AN:

26118

East Asian (EAS)

AF:

0.0773

AC:

3069

AN:

39696

South Asian (SAS)

AF:

0.215

AC:

18537

AN:

86182

European-Finnish (FIN)

AF:

0.299

AC:

15975

AN:

53414

Middle Eastern (MID)

AF:

0.302

AC:

1742

AN:

5766

European-Non Finnish (NFE)

AF:

0.246

AC:

273117

AN:

1111122

Other (OTH)

AF:

0.260

AC:

15688

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

12765

25529

38294

51058

63823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9148

18296

27444

36592

45740

<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:

0.338

AC:

51280

AN:

151666

Hom.:

10668

Cov.:

AF XY:

0.334

AC XY:

24777

AN XY:

74100

show subpopulations

African (AFR)

AF:

0.585

AC:

24148

AN:

41290

American (AMR)

AF:

0.223

AC:

3391

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

941

AN:

3462

East Asian (EAS)

AF:

0.0650

AC:

336

AN:

5172

South Asian (SAS)

AF:

0.187

AC:

902

AN:

4816

European-Finnish (FIN)

AF:

0.304

AC:

3189

AN:

10504

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17351

AN:

67896

Other (OTH)

AF:

0.308

AC:

649

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1502

3003

4505

6006

7508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.279

Hom.:

9188

Bravo

AF:

0.343

Asia WGS

AF:

0.175

AC:

606

AN:

3478

EpiCase

AF:

0.253

EpiControl

AF:

0.247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=50/50

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00071

dbscSNV1_RF

Benign

0.0040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over