9-7799581-C-T

Variant names:

• chr9-7799581-C-T
• rs761827796
• NM_033428.3:c.154G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033428.3(DMAC1):​c.154G>A​(p.Val52Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. 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. V52L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DMAC1 NM_033428.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 0 publications found

Genes affected

DMAC1 (HGNC:30536): (distal membrane arm assembly component 1) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrial inner membrane. 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 (MetaRNN=0.10427764).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033428.3. 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
	DMAC1	NM_033428.3	MANE Select	c.154G>A	p.Val52Met	missense	Exon 1 of 2	NP_219500.1	Q96GE9-2
	DMAC1	NM_001318059.2		c.154G>A	p.Val52Met	missense	Exon 1 of 2	NP_001304988.1
	DMAC1	NM_001318058.2		c.154G>A	p.Val52Met	missense	Exon 1 of 2	NP_001304987.1	Q96GE9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMAC1	ENST00000358227.5	TSL:1 MANE Select	c.154G>A	p.Val52Met	missense	Exon 1 of 2	ENSP00000350961.4	Q96GE9-2
	DMAC1	ENST00000929251.1		c.154G>A	p.Val52Met	missense	Exon 1 of 2	ENSP00000599310.1
	DMAC1	ENST00000880535.1		c.52+102G>A		intron	N/A	ENSP00000550594.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	5.3
DANN	Uncertain	0.98
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.98	T
PhyloP100		-1.7
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.059
Sift	Benign	0.066	T
Sift4G	Uncertain	0.011	D
Polyphen		0.059	B
Vest4		0.26
MutPred		0.35		Loss of sheet (P = 0.0084)
MVP		0.24
MPC		0.20
ClinPred		0.39	T
GERP RS		-2.2
PromoterAI		-0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.71
Mutation Taster		=96/4	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

Other links and lift over

dbSNP: rs761827796; hg19: chr9-7799581;