NM_018035.3:c.692T>C

Variant names:

• chr19-41432313-A-G
• NM_018035.3:c.692T>C
• DMAC2 p.Val231Ala

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018035.3(DMAC2):​c.692T>C​(p.Val231Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V231V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DMAC2 NM_018035.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.42
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.836

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.692T>C	p.Val231Ala	missense	Exon 6 of 6	NP_060505.2	Q9NW81-1
	DMAC2	NM_001167867.2		c.710T>C	p.Val237Ala	missense	Exon 6 of 6	NP_001161339.1	Q9NW81-4
	DMAC2	NM_001320840.2		c.629T>C	p.Val210Ala	missense	Exon 5 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.692T>C	p.Val231Ala	missense	Exon 6 of 6	ENSP00000221943.8	Q9NW81-1
	DMAC2	ENST00000438807.7	TSL:1	c.448T>C	p.Leu150Leu	synonymous	Exon 4 of 4	ENSP00000397413.3	Q9NW81-2
	DMAC2	ENST00000417807.7	TSL:2	c.710T>C	p.Val237Ala	missense	Exon 6 of 6	ENSP00000403910.2	Q9NW81-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.55
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.68	T
PhyloP100		5.4
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.61
Mutation Taster		=77/23	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-41938218;