rs367830809

Variant names:

• chr19-41433321-C-A
• rs367830809
• NM_018035.3:c.547G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-41433321-C-A
• chr19-41433321-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018035.3(DMAC2):​c.547G>T​(p.Gly183Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,194 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DMAC2 NM_018035.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMAC2	NM_018035.3	c.547G>T	p.Gly183Cys	missense_variant	Exon 5 of 6	ENST00000221943.14	NP_060505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMAC2	ENST00000221943.14	c.547G>T	p.Gly183Cys	missense_variant	Exon 5 of 6	2	NM_018035.3	ENSP00000221943.8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247648 Hom.: 0 AF XY: 0.00000744 AC XY: 1 AN XY: 134430

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459194 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726062

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;.;.;T;.
Eigen	Benign	-0.044
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.85	D;D;D;D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.48	T;T;T;T;T;T
MetaSVM	Benign	-0.53	T
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.5	D;.;D;.;.;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.0050	D;.;D;.;.;.
Sift4G	Uncertain	0.0020	D;D;D;D;D;.
Polyphen		1.0	D;.;.;D;.;.
Vest4		0.60
MutPred		0.57		Loss of loop (P = 0.1242);.;.;.;.;.;
MVP		0.58
MPC		0.72
ClinPred		0.91	D
GERP RS		3.4
Varity_R		0.33
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs367830809; hg19: chr19-41939226;