20-35699435-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_080748.3(ROMO1):c.-22C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,184,152 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0084 (19 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (14 hom.)
• Consequence: ROMO1 NM_080748.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.585

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 20-35699435-C-T is Benign according to our data. Variant chr20-35699435-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316288.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00835 (1272/152334) while in subpopulation AFR AF= 0.0289 (1201/41584). AF 95% confidence interval is 0.0275. There are 19 homozygotes in gnomad4. There are 598 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROMO1	NM_080748.3	c.-22C>T		5_prime_UTR_variant	1/3	ENST00000374077.8
ROMO1	XM_017027678.2	c.-17C>T		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROMO1	ENST00000374077.8	c.-22C>T		5_prime_UTR_variant	1/3	1	NM_080748.3	P1

Frequencies

GnomAD3 genomes AF: 0.00836 AC: 1273 AN: 152216 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.000753 AC: 777 AN: 1031818 Hom.: 14 Cov.: 14 AF XY: 0.000684 AC XY: 349 AN XY: 510296

Gnomad4 AFR exome AF: 0.0284

Gnomad4 AMR exome AF: 0.00142

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000167

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000474

Gnomad4 OTH exome AF: 0.00160

GnomAD4 genome AF: 0.00835 AC: 1272 AN: 152334 Hom.: 19 Cov.: 32 AF XY: 0.00803 AC XY: 598 AN XY: 74472

Gnomad4 AFR AF: 0.0289

Gnomad4 AMR AF: 0.00300

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00321 Hom.: 3

Bravo AF: 0.00998

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	18
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6119641; hg19: chr20-34287357;