NM_080748.3:c.8T>A

Variant names:

• chr20-35699640-T-A
• rs764867344
• NM_080748.3:c.8T>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_080748.3(ROMO1):​c.8T>A​(p.Val3Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: ROMO1 NM_080748.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.58

Genes affected

ROMO1 (HGNC:16185): (reactive oxygen species modulator 1) The protein encoded by this gene is a mitochondrial membrane protein that is responsible for increasing the level of reactive oxygen species (ROS) in cells. The protein also has antimicrobial activity against a variety of bacteria by inducing bacterial membrane breakage. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROMO1	NM_080748.3	c.8T>A	p.Val3Glu	missense_variant	Exon 2 of 3	ENST00000374077.8	NP_542786.1
ROMO1	XM_017027678.2	c.8T>A	p.Val3Glu	missense_variant	Exon 2 of 3		XP_016883167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROMO1	ENST00000374077.8	c.8T>A	p.Val3Glu	missense_variant	Exon 2 of 3	1	NM_080748.3	ENSP00000363190.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T;.;T;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.85	.;.;D;.;T
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.80	D;D;D;D;D
MetaSVM	Benign	-0.43	T
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.2	N;N;N;N;N
REVEL	Uncertain	0.37
Sift	Benign	0.059	T;T;D;T;T
Sift4G	Uncertain	0.018	D;D;D;D;D
Polyphen		1.0	D;D;.;D;D
Vest4		0.80
MutPred		0.34		Gain of solvent accessibility (P = 9e-04);Gain of solvent accessibility (P = 9e-04);Gain of solvent accessibility (P = 9e-04);Gain of solvent accessibility (P = 9e-04);Gain of solvent accessibility (P = 9e-04);
MVP		0.49
MPC		2.5
ClinPred		0.99	D
GERP RS		5.1
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.64
gMVP		0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs764867344; hg19: chr20-34287562;