rs144637709

Variant names:

• chr19-41433291-C-T
• rs144637709
• NM_018035.3:c.577G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_018035.3(DMAC2):​c.577G>A​(p.Ala193Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000378 in 1,608,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00039 (0 hom.)
• Consequence: DMAC2 NM_018035.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.49
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34862763).

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.577G>A	p.Ala193Thr	missense	Exon 5 of 6	NP_060505.2	Q9NW81-1
	DMAC2	NM_001167867.2		c.595G>A	p.Ala199Thr	missense	Exon 5 of 6	NP_001161339.1	Q9NW81-4
	DMAC2	NM_001320840.2		c.514G>A	p.Ala172Thr	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.577G>A	p.Ala193Thr	missense	Exon 5 of 6	ENSP00000221943.8	Q9NW81-1
	DMAC2	ENST00000438807.7	TSL:1	c.352+246G>A		intron	N/A	ENSP00000397413.3	Q9NW81-2
	DMAC2	ENST00000417807.7	TSL:2	c.595G>A	p.Ala199Thr	missense	Exon 5 of 6	ENSP00000403910.2	Q9NW81-4

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152136 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000290 AC: 71 AN: 244540 AF XY: 0.000308

Gnomad AFR exome AF: 0.0000641

Gnomad AMR exome AF: 0.000378

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000486

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.000390 AC: 568 AN: 1456794 Hom.: 0 Cov.: 30 AF XY: 0.000389 AC XY: 282 AN XY: 724892

African (AFR) AF: 0.0000299 AC: 1 AN: 33440

American (AMR) AF: 0.000426 AC: 19 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 86060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50436

Middle Eastern (MID) AF: 0.000589 AC: 3 AN: 5094

European-Non Finnish (NFE) AF: 0.000466 AC: 518 AN: 1111242

Other (OTH) AF: 0.000382 AC: 23 AN: 60180

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152136 Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 12 AN XY: 74318

African (AFR) AF: 0.0000241 AC: 1 AN: 41408

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000483 Hom.: 0

Bravo AF: 0.000329

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000198 AC: 24

EpiCase AF: 0.000600

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.61	T
PhyloP100		4.5
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.23
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.61
MVP		0.66
MPC		0.67
ClinPred		0.36	T
GERP RS		4.4
Varity_R		0.24
gMVP		0.36
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs144637709; hg19: chr19-41939196;