Variant chr4-99901104-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_001031723.4(DNAJB14):c.1064G>A(p.Arg355Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,458,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

DNAJB14
NM_001031723.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.80

Variant links:

Genes affected

DNAJB14 (HGNC:25881): (DnaJ heat shock protein family (Hsp40) member B14) Enables Hsp70 protein binding activity. Involved in cellular protein-containing complex assembly and chaperone cofactor-dependent protein refolding. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

DNAJB14 links:

DNAJB14 (HGNC:):

DNAJB14 links:

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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=0.17046028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB14	NM_001031723.4 linkuse as main transcript	c.1064G>A	p.Arg355Gln	missense_variant	8/8	ENST00000442697.7	NP_001026893.1	Q8TBM8-1
DNAJB14	NM_001278310.2 linkuse as main transcript	c.863G>A	p.Arg288Gln	missense_variant	7/7		NP_001265239.1	Q8TBM8
DNAJB14	XM_047416184.1 linkuse as main transcript	c.809G>A	p.Arg270Gln	missense_variant	8/8		XP_047272140.1
DNAJB14	XM_047416185.1 linkuse as main transcript	c.800G>A	p.Arg267Gln	missense_variant	9/9		XP_047272141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB14	ENST00000442697.7 linkuse as main transcript	c.1064G>A	p.Arg355Gln	missense_variant	8/8	1	NM_001031723.4	ENSP00000404381.2		Q8TBM8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

250224

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1458690

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

725654

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

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.1064G>A (p.R355Q) alteration is located in exon 8 (coding exon 8) of the DNAJB14 gene. This alteration results from a G to A substitution at nucleotide position 1064, causing the arginine (R) at amino acid position 355 to be replaced by a glutamine (Q). 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

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0066

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.41

PROVEAN

Benign

0.060

REVEL

Benign

0.077

Sift

Benign

0.34

Sift4G

Benign

0.25

Polyphen

0.47

Vest4

0.24

MutPred

0.62

Loss of MoRF binding (P = 0.0379);

MVP

0.60

MPC

0.68

ClinPred

0.17

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.070

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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