Variant 12-49349314-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001304944.2(DNAJC22):c.442C>T(p.Arg148Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

DNAJC22
NM_001304944.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67

Variant links:

Genes affected

DNAJC22 (HGNC:25802): (DnaJ heat shock protein family (Hsp40) member C22) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02909863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC22	NM_001304944.2 linkuse as main transcript	c.442C>T	p.Arg148Cys	missense_variant	3/4	ENST00000549441.7	NP_001291873.1	Q8N4W6A0A024R0Z2
DNAJC22	NM_024902.4 linkuse as main transcript	c.442C>T	p.Arg148Cys	missense_variant	2/3		NP_079178.2	Q8N4W6A0A024R0Z2
DNAJC22	XM_047429555.1 linkuse as main transcript	c.442C>T	p.Arg148Cys	missense_variant	3/6		XP_047285511.1
DNAJC22	XM_047429556.1 linkuse as main transcript	c.442C>T	p.Arg148Cys	missense_variant	3/5		XP_047285512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAJC22	ENST00000549441.7 linkuse as main transcript	c.442C>T	p.Arg148Cys	missense_variant	3/4	2	NM_001304944.2	ENSP00000446830.1	Q8N4W6
DNAJC22	ENST00000395069.3 linkuse as main transcript	c.442C>T	p.Arg148Cys	missense_variant	2/3	1		ENSP00000378508.2	Q8N4W6
DNAJC22	ENST00000647553.1 linkuse as main transcript	n.442C>T		non_coding_transcript_exon_variant	2/4			ENSP00000498036.1	Q8N4W6

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

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:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000799

AC:

AN:

250272

Hom.:

AF XY:

0.0000739

AC XY:

AN XY:

135292

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1461062

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726808

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000197

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000645

Hom.:

Bravo

AF:

0.000208

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

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

Mar 29, 2024

The c.442C>T (p.R148C) alteration is located in exon 2 (coding exon 1) of the DNAJC22 gene. This alteration results from a C to T substitution at nucleotide position 442, causing the arginine (R) at amino acid position 148 to be replaced by a cysteine (C). 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

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.068

T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.79

M_CAP

Benign

0.019

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.013

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.022

B;B

Vest4

0.47

MVP

0.59

MPC

0.031

ClinPred

0.11

GERP RS

3.0

Varity_R

0.22

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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