NM_080748.3:c.112G>C

Variant names:

• chr20-35699744-G-C
• rs1415900079
• NM_080748.3:c.112G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_080748.3(ROMO1):​c.112G>C​(p.Gly38Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ROMO1 NM_080748.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.45
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.945

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080748.3. 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
	ROMO1	NM_080748.3	MANE Select	c.112G>C	p.Gly38Arg	missense	Exon 2 of 3	NP_542786.1	P60602-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROMO1	ENST00000374077.8	TSL:1 MANE Select	c.112G>C	p.Gly38Arg	missense	Exon 2 of 3	ENSP00000363190.3	P60602-1
	ROMO1	ENST00000336695.4	TSL:1	c.112G>C	p.Gly38Arg	missense	Exon 1 of 2	ENSP00000338293.4	P60602-1
	ROMO1	ENST00000374078.5	TSL:1	c.112G>C	p.Gly38Arg	missense	Exon 2 of 3	ENSP00000363191.1	P60602-1

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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.29	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.61	T
PhyloP100		9.4
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-7.3	D
REVEL	Pathogenic	0.72
Sift	Benign	0.054	T
Sift4G	Benign	0.099	T
Polyphen		0.23	B
Vest4		0.99
MutPred		0.80		Gain of MoRF binding (P = 0.0093)
MVP		0.67
MPC		1.3
ClinPred		1.0	D
GERP RS		4.3
PromoterAI		-0.073	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.97
gMVP		0.99
Mutation Taster		=32/68	disease causing

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: rs1415900079; hg19: chr20-34287666;