Genetic Variant DNAJC18:p.Met191Ile (chr5-139425101-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_152686.4(DNAJC18):c.573G>A(p.Met191Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,611,764 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: 31)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

DNAJC18
NM_152686.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.85

Publications

0 publications found

Variant links:

Genes affected

DNAJC18 (HGNC:28429): (DnaJ heat shock protein family (Hsp40) member C18) Predicted to enable Hsp70 protein binding activity. Predicted to be involved in cellular response to misfolded protein; chaperone cofactor-dependent protein refolding; and ubiquitin-dependent ERAD pathway. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC18 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=0.24820101).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152686.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC18	NM_152686.4	MANE Select	c.573G>A	p.Met191Ile	missense	Exon 5 of 8	NP_689899.1	Q9H819

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAJC18	ENST00000302060.10	TSL:1 MANE Select	c.573G>A	p.Met191Ile	missense	Exon 5 of 8	ENSP00000302843.5	Q9H819
DNAJC18	ENST00000928618.1		c.600G>A	p.Met200Ile	missense	Exon 6 of 9	ENSP00000598677.1
DNAJC18	ENST00000508445.5	TSL:3	c.72G>A	p.Met24Ile	missense	Exon 2 of 6	ENSP00000426338.1	H0YA78

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00000685

AC:

AN:

1459604

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726106

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33448

American (AMR)

AF:

0.00

AC:

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26016

East Asian (EAS)

AF:

0.00

AC:

AN:

39596

South Asian (SAS)

AF:

0.00

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1110348

Other (OTH)

AF:

0.00

AC:

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

152160

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.0000655

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

Pathogenic

0.62

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.013

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

3.9

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.0

REVEL

Benign

0.11

Sift

Benign

0.19

Sift4G

Benign

0.31

Polyphen

0.78

Vest4

0.80

MutPred

0.38

Loss of phosphorylation at T196 (P = 0.0989)

MVP

0.61

MPC

0.50

ClinPred

0.65

GERP RS

5.7

PromoterAI

-0.0072

Neutral

(source)

Varity_R

0.13

gMVP

0.75

Mutation Taster

=94/6

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over