Variant 2-24957146-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_016544.3(DNAJC27):c.425G>A(p.Arg142His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000081 in 1,604,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

DNAJC27
NM_016544.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.964

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC27	NM_016544.3 linkuse as main transcript	c.425G>A	p.Arg142His	missense_variant	5/7	ENST00000264711.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC27	ENST00000264711.7 linkuse as main transcript	c.425G>A	p.Arg142His	missense_variant	5/7	1	NM_016544.3	P1	Q9NZQ0-1
DNAJC27	ENST00000534855.5 linkuse as main transcript	c.425G>A	p.Arg142His	missense_variant	5/6	1			Q9NZQ0-3
DNAJC27	ENST00000494239.5 linkuse as main transcript	n.399G>A		non_coding_transcript_exon_variant	5/6	4
DNAJC27	ENST00000380809.7 linkuse as main transcript	c.*207G>A		3_prime_UTR_variant, NMD_transcript_variant	6/9	2			Q9NZQ0-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000208

AC:

AN:

240956

Hom.:

AF XY:

0.00000765

AC XY:

AN XY:

130758

show subpopulations

Gnomad AFR exome

AF:

0.0000631

Gnomad AMR exome

AF:

0.0000323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000343

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000689

AC:

AN:

1452278

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

722500

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000241

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000473

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.425G>A (p.R142H) alteration is located in exon 5 (coding exon 5) of the DNAJC27 gene. This alteration results from a G to A substitution at nucleotide position 425, causing the arginine (R) at amino acid position 142 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Pathogenic

0.30

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Uncertain

0.73

D;.

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

D;D

M_CAP

Uncertain

0.26

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Uncertain

0.77

MutationAssessor

Pathogenic

3.4

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-4.6

D;N

REVEL

Pathogenic

0.89

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;D

Vest4

0.71

MutPred

0.92

Gain of disorder (P = 0.1175);Gain of disorder (P = 0.1175);

MVP

0.90

MPC

0.94

ClinPred

0.99

GERP RS

4.9

Varity_R

0.60

gMVP

0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over