chr1-6644613-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018198.4(DNAJC11):​c.1042G>A​(p.Val348Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DNAJC11
NM_018198.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02
Variant links:
Genes affected
DNAJC11 (HGNC:25570): (DnaJ heat shock protein family (Hsp40) member C11) Involved in cristae formation. Located in mitochondrial outer membrane and nuclear speck. Part of MIB complex. Colocalizes with MICOS complex and SAM complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06353381).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNAJC11NM_018198.4 linkuse as main transcriptc.1042G>A p.Val348Ile missense_variant 10/16 ENST00000377577.10
DNAJC11XM_047424842.1 linkuse as main transcriptc.772G>A p.Val258Ile missense_variant 8/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNAJC11ENST00000377577.10 linkuse as main transcriptc.1042G>A p.Val348Ile missense_variant 10/161 NM_018198.4 P1Q9NVH1-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251470
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461886
Hom.:
0
Cov.:
34
AF XY:
0.00000275
AC XY:
2
AN XY:
727246
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsJun 30, 2023The c.1042G>A (p.V348I) alteration is located in exon 10 (coding exon 10) of the DNAJC11 gene. This alteration results from a G to A substitution at nucleotide position 1042, causing the valine (V) at amino acid position 348 to be replaced by an isoleucine (I). 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
0.064
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
14
DANN
Benign
0.97
DEOGEN2
Benign
0.010
T;.
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.68
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.064
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.035
N;N
MutationTaster
Benign
0.94
D;D;D;D;D
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.28
N;N
REVEL
Benign
0.067
Sift
Benign
0.21
T;T
Sift4G
Benign
0.24
T;T
Polyphen
0.0010
B;B
Vest4
0.11
MutPred
0.30
Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP
0.093
MPC
0.39
ClinPred
0.18
T
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.019
gMVP
0.22

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.

Other links and lift over

dbSNP: rs748488397; hg19: chr1-6704673; API