19-41433393-A-T

Variant names:

• chr19-41433393-A-T
• NM_018035.3:c.475T>A
• DMAC2 p.Cys159Ser

Variant summary

Our verdict is

Uncertain significance

0 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018035.3(DMAC2):​c.475T>A​(p.Cys159Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DMAC2 NM_018035.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.073).

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.475T>A	p.Cys159Ser	missense	Exon 5 of 6	NP_060505.2	Q9NW81-1
	DMAC2	NM_001167867.2		c.493T>A	p.Cys165Ser	missense	Exon 5 of 6	NP_001161339.1	Q9NW81-4
	DMAC2	NM_001320840.2		c.412T>A	p.Cys138Ser	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.475T>A	p.Cys159Ser	missense	Exon 5 of 6	ENSP00000221943.8	Q9NW81-1
	DMAC2	ENST00000438807.7	TSL:1	c.352+144T>A		intron	N/A	ENSP00000397413.3	Q9NW81-2
	DMAC2	ENST00000417807.7	TSL:2	c.493T>A	p.Cys165Ser	missense	Exon 5 of 6	ENSP00000403910.2	Q9NW81-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	20
DANN	Benign	0.82
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.088	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
PhyloP100		4.0
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.73	N
REVEL	Benign	0.073
Sift	Benign	0.14	T
Sift4G	Benign	0.14	T
Varity_R		0.060
gMVP		0.57
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr19-41939298;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline