Variant 13-43068984-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000379221.4(DNAJC15):c.215C>T(p.Ala72Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,220 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 6.8e-7 ( 0 hom. )

Consequence

DNAJC15
ENST00000379221.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.45

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:

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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=0.34671813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC15	NM_013238.3 linkuse as main transcript	c.215C>T	p.Ala72Val	missense_variant	3/6	ENST00000379221.4	NP_037370.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC15	ENST00000379221.4 linkuse as main transcript	c.215C>T	p.Ala72Val	missense_variant	3/6	1	NM_013238.3	ENSP00000368523	P1
DNAJC15	ENST00000474320.1 linkuse as main transcript	n.639C>T		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460220

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726424

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

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

Aug 17, 2022

The c.215C>T (p.A72V) alteration is located in exon 3 (coding exon 3) of the DNAJC15 gene. This alteration results from a C to T substitution at nucleotide position 215, causing the alanine (A) at amino acid position 72 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0054

Eigen

Benign

-0.16

Eigen_PC

Benign

0.0077

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.78

M_CAP

Benign

0.0097

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Benign

0.36

REVEL

Benign

0.033

Sift

Benign

0.55

Sift4G

Benign

0.51

Polyphen

0.0020

Vest4

0.70

MutPred

0.38

Gain of methylation at K73 (P = 0.0368);

MVP

0.25

MPC

0.051

ClinPred

0.89

GERP RS

4.4

Varity_R

0.060

gMVP

0.62

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