Variant 12-55828024-C-A 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_032364.6(DNAJC14):c.635G>T(p.Arg212Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAJC14
NM_032364.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02

Variant links:

Genes affected

DNAJC14 (HGNC:24581): (DnaJ heat shock protein family (Hsp40) member C14) Predicted to be involved in protein transport. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC14 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=0.1310665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC14	NM_032364.6 linkuse as main transcript	c.635G>T	p.Arg212Leu	missense_variant	2/7	ENST00000678005.2	NP_115740.5	Q6Y2X3A0A024RB64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC14	ENST00000678005.2 linkuse as main transcript	c.635G>T	p.Arg212Leu	missense_variant	2/7		NM_032364.6	ENSP00000504134.1		Q6Y2X3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250702

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135538

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461114

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726876

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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.:

Alfa

AF:

0.0000283

Hom.:

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

Nov 02, 2023

The c.635G>T (p.R212L) alteration is located in exon 2 (coding exon 1) of the DNAJC14 gene. This alteration results from a G to T substitution at nucleotide position 635, causing the arginine (R) at amino acid position 212 to be replaced by a leucine (L). 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

0.19

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.085

T;T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.80

T;.;.

M_CAP

Benign

0.017

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;M;M

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.16

Sift

Uncertain

0.015

D;D;D

Sift4G

Uncertain

0.037

D;D;D

Polyphen

0.48

P;P;P

Vest4

0.54

MutPred

0.26

Gain of catalytic residue at R212 (P = 0.0101);Gain of catalytic residue at R212 (P = 0.0101);Gain of catalytic residue at R212 (P = 0.0101);

MVP

0.22

MPC

0.28

ClinPred

0.26

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.18

gMVP

0.24

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