Variant 11-64233967-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005528.4(DNAJC4):c.601C>T(p.Arg201Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,724 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: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

DNAJC4
NM_005528.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.150

Variant links:

Genes affected

DNAJC4 (HGNC:5271): (DnaJ heat shock protein family (Hsp40) member C4) Predicted to be involved in response to unfolded protein. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC4 links:

DNAJC4 (HGNC:):

DNAJC4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1439845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC4	NM_005528.4 linkuse as main transcript	c.601C>T	p.Arg201Trp	missense_variant	5/6	ENST00000628077.3	NP_005519.2	Q9NNZ3
DNAJC4	NM_001307980.1 linkuse as main transcript	c.604C>T	p.Arg202Trp	missense_variant	5/5		NP_001294909.1	Q9NNZ3J3KNJ8Q6PIN0
DNAJC4	NM_001307981.1 linkuse as main transcript	c.601C>T	p.Arg201Trp	missense_variant	5/5		NP_001294910.1	Q9NNZ3Q86VG4
DNAJC4	XM_047426865.1 linkuse as main transcript	c.604C>T	p.Arg202Trp	missense_variant	5/6		XP_047282821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC4	ENST00000628077.3 linkuse as main transcript	c.601C>T	p.Arg201Trp	missense_variant	5/6	5	NM_005528.4	ENSP00000486499.2		Q9NNZ3Q96FY5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000521

AC:

AN:

249452

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

135390

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000261

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:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461724

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000662

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

Feb 28, 2023

The c.601C>T (p.R201W) alteration is located in exon 6 (coding exon 5) of the DNAJC4 gene. This alteration results from a C to T substitution at nucleotide position 601, causing the arginine (R) at amino acid position 201 to be replaced by a tryptophan (W). 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

0.67

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.90

D;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.7

D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.15

B;.

Vest4

0.55

MutPred

0.48

Loss of disorder (P = 0.0032);.;

MVP

0.33

MPC

0.63

ClinPred

0.52

GERP RS

-0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.46

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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