Genetic Variant DNAJC27:p.Met22Thr (chr2-24971840-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016544.3(DNAJC27):c.65T>C(p.Met22Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000373 in 1,609,196 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M22L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

DNAJC27
NM_016544.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.02

Publications

0 publications found

Variant links:

Genes affected

DNAJC27 (HGNC:30290): (DnaJ heat shock protein family (Hsp40) member C27) Predicted to enable GTPase activity. Predicted to be involved in intracellular protein transport and positive regulation of MAPK cascade. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC27 links:

DNAJC27-AS1 (HGNC:42943): (DNAJC27 antisense RNA 1)

DNAJC27-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016544.3. 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
	DNAJC27	NM_016544.3	MANE Select	c.65T>C	p.Met22Thr	missense	Exon 1 of 7	NP_057628.1	Q9NZQ0-1
	DNAJC27	NM_001198559.1		c.65T>C	p.Met22Thr	missense	Exon 1 of 6	NP_001185488.1	Q9NZQ0-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAJC27	ENST00000264711.7	TSL:1 MANE Select	c.65T>C	p.Met22Thr	missense	Exon 1 of 7	ENSP00000264711.2	Q9NZQ0-1
DNAJC27	ENST00000534855.5	TSL:1	c.65T>C	p.Met22Thr	missense	Exon 1 of 6	ENSP00000440086.2	Q9NZQ0-3
DNAJC27	ENST00000380809.7	TSL:2	n.65T>C		non_coding_transcript_exon	Exon 1 of 9	ENSP00000370187.3	Q9NZQ0-2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

GnomAD2 exomes

AF:

0.0000204

AC:

AN:

245324

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000255

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000350

AC:

AN:

1457068

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

724820

show subpopulations

African (AFR)

AF:

0.0000605

AC:

AN:

33084

American (AMR)

AF:

0.0000226

AC:

AN:

44182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26018

East Asian (EAS)

AF:

0.00

AC:

AN:

39306

South Asian (SAS)

AF:

0.00

AC:

AN:

85552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000378

AC:

AN:

1110252

Other (OTH)

AF:

0.0000996

AC:

AN:

60230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

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:

0.0000592

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41420

American (AMR)

AF:

0.000131

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

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: 0.536

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:

0.000109

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000330

AC:

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

0.84

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.39

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.54

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.077

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-0.42

MutationAssessor

Benign

1.8

PhyloP100

7.0

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-4.5

REVEL

Pathogenic

0.65

Sift

Benign

0.040

Sift4G

Uncertain

0.032

Polyphen

0.018

Vest4

0.78

MVP

0.79

MPC

0.29

ClinPred

0.47

GERP RS

6.0

PromoterAI

0.20

Neutral

(source)

Varity_R

0.78

gMVP

0.73

Mutation Taster

=69/31

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