Genetic Variant DNAJC14:p.Arg698Lys (chr12-55821993-C-T) – 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_032364.6(DNAJC14):c.2093G>A(p.Arg698Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,612,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DNAJC14
NM_032364.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56

Publications

0 publications found

Variant links:

Genes affected

DNAJC14 (HGNC:24581): (DnaJ heat shock protein family (Hsp40) member C14) Predicted to be involved in protein transport. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC14 links:

ENSG00000257390 (HGNC:):

ENSG00000257390 links:

ORMDL2 (HGNC:16037): (ORMDL sphingolipid biosynthesis regulator 2) Involved in ceramide metabolic process. Acts upstream of or within negative regulation of ceramide biosynthetic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ORMDL2 links:

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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=0.20465356).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032364.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAJC14	NM_032364.6	MANE Select	c.2093G>A	p.Arg698Lys	missense	Exon 7 of 7	NP_115740.5
DNAJC14	NM_001394687.1		c.2093G>A	p.Arg698Lys	missense	Exon 7 of 7	NP_001381616.1	Q6Y2X3
DNAJC14	NM_001394688.1		c.2093G>A	p.Arg698Lys	missense	Exon 7 of 7	NP_001381617.1	Q6Y2X3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAJC14	ENST00000678005.2	MANE Select	c.2093G>A	p.Arg698Lys	missense	Exon 7 of 7	ENSP00000504134.1	Q6Y2X3
ENSG00000257390	ENST00000546837.5	TSL:2	c.972+8G>A		splice_region intron	N/A	ENSP00000447000.1	H0YHG0
DNAJC14	ENST00000317287.5	TSL:2	c.2093G>A	p.Arg698Lys	missense	Exon 7 of 7	ENSP00000317500.5	Q6Y2X3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460152

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726432

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33380

American (AMR)

AF:

0.00

AC:

AN:

44316

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26000

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

86048

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111292

Other (OTH)

AF:

0.00

AC:

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.056

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.72

M_CAP

Benign

0.0087

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

4.6

PROVEAN

Benign

-0.78

REVEL

Benign

0.079

Sift

Benign

0.25

Sift4G

Benign

0.30

Polyphen

0.82

Vest4

0.14

MutPred

0.19

Gain of methylation at R698 (P = 0.0053)

MVP

0.33

MPC

1.2

ClinPred

0.87

GERP RS

5.6

Varity_R

0.28

gMVP

0.23

Mutation Taster

=80/20

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over