Genetic Variant RMI1:p.Val144Ile (chr9-84001416-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001358291.2(RMI1):c.430G>A(p.Val144Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

RMI1
NM_001358291.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.571

Variant links:

Genes affected

RMI1 (HGNC:25764): (RecQ mediated genome instability 1) Predicted to enable nucleotide binding activity. Predicted to be involved in double-strand break repair via homologous recombination and resolution of meiotic recombination intermediates. Predicted to act upstream of or within glucose homeostasis; reduction of food intake in response to dietary excess; and response to glucose. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

RMI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044279307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMI1	NM_001358291.2 link	c.430G>A	p.Val144Ile	missense_variant	Exon 3 of 3	ENST00000445877.6	NP_001345220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMI1	ENST00000445877.6 link	c.430G>A	p.Val144Ile	missense_variant	Exon 3 of 3	1	NM_001358291.2	ENSP00000402433.2		Q9H9A7A0A0A0MSU3
RMI1	ENST00000325875.7 link	c.430G>A	p.Val144Ile	missense_variant	Exon 3 of 3	2		ENSP00000317039.3		Q9H9A7

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251000

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.430G>A (p.V144I) alteration is located in exon 3 (coding exon 1) of the RMI1 gene. This alteration results from a G to A substitution at nucleotide position 430, causing the valine (V) at amino acid position 144 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.60

N;N

REVEL

Benign

0.047

Sift

Benign

0.16

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.0010

.;B

Vest4

0.037

MVP

0.13

MPC

0.060

ClinPred

0.014

GERP RS

0.42

Varity_R

0.020

gMVP

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over