20-35699657-G-A
Position:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
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
NM_080748.3 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 9.45
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -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 id is 1318406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ROMO1 | NM_080748.3 | c.25G>A | p.Gly9Arg | missense_variant | 2/3 | ENST00000374077.8 | NP_542786.1 | |
ROMO1 | XM_017027678.2 | c.25G>A | p.Gly9Arg | missense_variant | 2/3 | XP_016883167.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ROMO1 | ENST00000374077.8 | c.25G>A | p.Gly9Arg | missense_variant | 2/3 | 1 | NM_080748.3 | ENSP00000363190 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00389 AC: 592AN: 152196Hom.: 3 Cov.: 32
GnomAD3 genomes
AF:
AC:
592
AN:
152196
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00101 AC: 254AN: 250562Hom.: 3 AF XY: 0.000693 AC XY: 94AN XY: 135570
GnomAD3 exomes
AF:
AC:
254
AN:
250562
Hom.:
AF XY:
AC XY:
94
AN XY:
135570
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000406 AC: 593AN: 1461242Hom.: 6 Cov.: 31 AF XY: 0.000337 AC XY: 245AN XY: 726986
GnomAD4 exome
AF:
AC:
593
AN:
1461242
Hom.:
Cov.:
31
AF XY:
AC XY:
245
AN XY:
726986
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00390 AC: 594AN: 152314Hom.: 3 Cov.: 32 AF XY: 0.00381 AC XY: 284AN XY: 74486
GnomAD4 genome
AF:
AC:
594
AN:
152314
Hom.:
Cov.:
32
AF XY:
AC XY:
284
AN XY:
74486
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
0
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
45
ESP6500EA
AF:
AC:
0
ExAC
AF:
AC:
132
Asia WGS
AF:
AC:
6
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 27, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;.;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;.;T;.;T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
D;D;T;D;D
Sift4G
Benign
T;T;T;T;T
Polyphen
D;D;.;D;D
Vest4
MutPred
Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at