9-84001057-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001358291.2(RMI1):​c.71C>T​(p.Pro24Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000837 in 1,613,782 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00029 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

RMI1
NM_001358291.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.828
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.007504195).
BP6
Variant 9-84001057-C-T is Benign according to our data. Variant chr9-84001057-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2274014.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RMI1NM_001358291.2 linkc.71C>T p.Pro24Leu missense_variant Exon 3 of 3 ENST00000445877.6 NP_001345220.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RMI1ENST00000445877.6 linkc.71C>T p.Pro24Leu missense_variant Exon 3 of 3 1 NM_001358291.2 ENSP00000402433.2 Q9H9A7A0A0A0MSU3
RMI1ENST00000325875.7 linkc.71C>T p.Pro24Leu missense_variant Exon 3 of 3 2 ENSP00000317039.3 Q9H9A7

Frequencies

GnomAD3 genomes
AF:
0.000289
AC:
44
AN:
152064
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00256
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:
0.00
GnomAD3 exomes
AF:
0.000163
AC:
41
AN:
251134
Hom.:
0
AF XY:
0.000184
AC XY:
25
AN XY:
135734
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.000954
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:
0.0000617
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000623
AC:
91
AN:
1461718
Hom.:
0
Cov.:
33
AF XY:
0.0000633
AC XY:
46
AN XY:
727160
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00121
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000252
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000289
AC:
44
AN:
152064
Hom.:
1
Cov.:
32
AF XY:
0.000296
AC XY:
22
AN XY:
74268
show subpopulations
Gnomad4 AFR
AF:
0.0000966
Gnomad4 AMR
AF:
0.00256
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:
0.00
Alfa
AF:
0.0000549
Hom.:
0
Bravo
AF:
0.000283
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000140
AC:
17
EpiCase
AF:
0.000218
EpiControl
AF:
0.000119

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Sep 09, 2021
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
1.2
DANN
Benign
0.49
DEOGEN2
Benign
0.028
T;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.50
T;T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.0075
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.58
.;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.65
N;N
REVEL
Benign
0.059
Sift
Benign
0.54
T;T
Sift4G
Benign
0.78
T;T
Polyphen
0.0010
.;B
Vest4
0.063
MVP
0.34
MPC
0.074
ClinPred
0.016
T
GERP RS
-4.7
Varity_R
0.077
gMVP
0.31

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.

Other links and lift over

dbSNP: rs373651916; hg19: chr9-86615972; API