Variant 11-64233974-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005528.4(DNAJC4):c.608G>C(p.Arg203Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,712 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: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DNAJC4
NM_005528.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.757

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC4	NM_005528.4 linkuse as main transcript	c.608G>C	p.Arg203Pro	missense_variant	5/6	ENST00000628077.3	NP_005519.2	Q9NNZ3
DNAJC4	NM_001307980.1 linkuse as main transcript	c.611G>C	p.Arg204Pro	missense_variant	5/5		NP_001294909.1	Q9NNZ3J3KNJ8Q6PIN0
DNAJC4	NM_001307981.1 linkuse as main transcript	c.608G>C	p.Arg203Pro	missense_variant	5/5		NP_001294910.1	Q9NNZ3Q86VG4
DNAJC4	XM_047426865.1 linkuse as main transcript	c.611G>C	p.Arg204Pro	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.608G>C	p.Arg203Pro	missense_variant	5/6	5	NM_005528.4	ENSP00000486499.2		Q9NNZ3Q96FY5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249454

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135384

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 30, 2023

The c.608G>C (p.R203P) alteration is located in exon 6 (coding exon 5) of the DNAJC4 gene. This alteration results from a G to C substitution at nucleotide position 608, causing the arginine (R) at amino acid position 203 to be replaced by a proline (P). 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

0.92

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-0.082

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.077

MetaRNN

Pathogenic

0.76

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-4.2

D;D

REVEL

Benign

0.28

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.98

D;.

Vest4

0.69

MutPred

0.56

Loss of helix (P = 0.0237);.;

MVP

0.52

MPC

0.76

ClinPred

0.98

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.89

gMVP

0.80

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