Variant 13-43065728-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_013238.3(DNAJC15):c.151G>A(p.Ala51Thr) variant causes a missense change. 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

DNAJC15
NM_013238.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.68

Variant links:

Genes affected

DNAJC15 (HGNC:20325): (DnaJ heat shock protein family (Hsp40) member C15) Predicted to enable ATPase activator activity. Predicted to be involved in protein import into mitochondrial matrix. Predicted to act upstream of or within several processes, including cellular response to starvation; negative regulation of mitochondrial electron transport, NADH to ubiquinone; and negative regulation of protein-containing complex assembly. Predicted to be located in mitochondrial inner membrane. Predicted to be part of PAM complex, Tim23 associated import motor. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC15 links:

DNAJC15 (HGNC:):

DNAJC15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27956912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC15	NM_013238.3 linkuse as main transcript	c.151G>A	p.Ala51Thr	missense_variant	2/6	ENST00000379221.4	NP_037370.2	Q9Y5T4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC15	ENST00000379221.4 linkuse as main transcript	c.151G>A	p.Ala51Thr	missense_variant	2/6	1	NM_013238.3	ENSP00000368523.2		Q9Y5T4
DNAJC15	ENST00000474320.1 linkuse as main transcript	n.575G>A		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460840

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726736

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.:

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

Jul 27, 2022

The c.151G>A (p.A51T) alteration is located in exon 2 (coding exon 2) of the DNAJC15 gene. This alteration results from a G to A substitution at nucleotide position 151, causing the alanine (A) at amino acid position 51 to be replaced by a threonine (T). 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

0.20

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

0.053

Eigen_PC

Benign

0.097

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.042

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.62

MutationAssessor

Pathogenic

3.3

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.1

REVEL

Benign

0.19

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.011

Polyphen

0.50

Vest4

0.41

MutPred

0.52

Gain of helix (P = 0.027);

MVP

0.30

MPC

0.076

ClinPred

0.98

GERP RS

3.9

Varity_R

0.081

gMVP

0.76

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over