rs1043413

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018035.3(DMAC2):​c.476G>T​(p.Cys159Phe) 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 1,461,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C159S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DMAC2
NM_018035.3 missense

Scores

2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.04
Variant links:
Genes affected
DMAC2 (HGNC:25496): (distal membrane arm assembly component 2) Involved in mitochondrial respiratory chain complex I assembly. Colocalizes with mitochondrial respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2022]

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=0.18242732).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DMAC2NM_018035.3 linkuse as main transcriptc.476G>T p.Cys159Phe missense_variant 5/6 ENST00000221943.14 NP_060505.2 Q9NW81-1A0A024R0K4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DMAC2ENST00000221943.14 linkuse as main transcriptc.476G>T p.Cys159Phe missense_variant 5/62 NM_018035.3 ENSP00000221943.8 Q9NW81-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461152
Hom.:
0
Cov.:
58
AF XY:
0.00000138
AC XY:
1
AN XY:
726900
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.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
21
DANN
Benign
0.96
DEOGEN2
Benign
0.013
T;.;.;.;T;.
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.42
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.44
T;T;T;T;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.18
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-2.1
N;.;N;.;.;.
REVEL
Benign
0.048
Sift
Uncertain
0.0030
D;.;D;.;.;.
Sift4G
Uncertain
0.0060
D;D;D;D;D;.
Polyphen
0.47
P;.;.;B;.;.
Vest4
0.19
MutPred
0.31
Gain of catalytic residue at C159 (P = 0.1123);.;.;.;.;.;
MVP
0.40
MPC
0.29
ClinPred
0.58
D
GERP RS
3.4
Varity_R
0.34
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1043413; hg19: chr19-41939297; API