rs73905935

Variant names:

• chr20-35699657-G-A
• rs73905935
• NM_080748.3:c.25G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-35699657-G-A
• chr20-35699657-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_080748.3(ROMO1):​c.25G>A​(p.Gly9Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000736 in 1,613,556 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (6 hom.)
• Consequence: ROMO1 NM_080748.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 9.45
• Publications: 3 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009671718).
• BP6: Variant 20-35699657-G-A is Benign according to our data. Variant chr20-35699657-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1318406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.25G>A	p.Gly9Arg	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.25G>A	p.Gly9Arg	missense	Exon 2 of 3	ENSP00000363190.3	P60602-1
	ROMO1	ENST00000336695.4	TSL:1	c.25G>A	p.Gly9Arg	missense	Exon 1 of 2	ENSP00000338293.4	P60602-1
	ROMO1	ENST00000374078.5	TSL:1	c.25G>A	p.Gly9Arg	missense	Exon 2 of 3	ENSP00000363191.1	P60602-1

Frequencies

GnomAD3 genomes AF: 0.00389 AC: 592 AN: 152196 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00235

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00101 AC: 254 AN: 250562 AF XY: 0.000693

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.000694

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000970

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000406 AC: 593 AN: 1461242 Hom.: 6 Cov.: 31 AF XY: 0.000337 AC XY: 245 AN XY: 726986

African (AFR) AF: 0.0122 AC: 407 AN: 33476

American (AMR) AF: 0.000984 AC: 44 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52834

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000612 AC: 68 AN: 1111972

Other (OTH) AF: 0.00103 AC: 62 AN: 60394

GnomAD4 genome AF: 0.00390 AC: 594 AN: 152314 Hom.: 3 Cov.: 32 AF XY: 0.00381 AC XY: 284 AN XY: 74486

African (AFR) AF: 0.0131 AC: 543 AN: 41584

American (AMR) AF: 0.00235 AC: 36 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68012

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00151 Hom.: 2

Bravo AF: 0.00430

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0102 AC: 45

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00109 AC: 132

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0097	T
MetaSVM	Benign	-0.68	T
PhyloP100		9.4
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.23
Sift	Benign	0.044	D
Sift4G	Benign	0.24	T
Polyphen		1.0	D
Vest4		0.87
MutPred		0.17		Loss of sheet (P = 0.0357)
MVP		0.14
MPC		2.2
ClinPred		0.033	T
GERP RS		5.2
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.51
gMVP		0.79
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs73905935; hg19: chr20-34287579;