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. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G183S) has been classified as Uncertain significance.

• 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
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018035.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMAC2	NM_018035.3	MANE Select	c.547G>T	p.Gly183Cys	missense	Exon 5 of 6	NP_060505.2	Q9NW81-1
	DMAC2	NM_001167867.2		c.565G>T	p.Gly189Cys	missense	Exon 5 of 6	NP_001161339.1	Q9NW81-4
	DMAC2	NM_001320840.2		c.484G>T	p.Gly162Cys	missense	Exon 4 of 5	NP_001307769.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMAC2	ENST00000221943.14	TSL:2 MANE Select	c.547G>T	p.Gly183Cys	missense	Exon 5 of 6	ENSP00000221943.8	Q9NW81-1
	DMAC2	ENST00000438807.7	TSL:1	c.352+216G>T		intron	N/A	ENSP00000397413.3	Q9NW81-2
	DMAC2	ENST00000417807.7	TSL:2	c.565G>T	p.Gly189Cys	missense	Exon 5 of 6	ENSP00000403910.2	Q9NW81-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247648 AF XY: 0.00000744

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5512

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111858

Other (OTH) AF: 0.00 AC: 0 AN: 60332

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.044
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.53	T
PhyloP100		1.3
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	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
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs367830809; hg19: chr19-41939226;