9-84001057-C-T

Variant names:

• chr9-84001057-C-T
• rs373651916
• NM_001358291.2:c.71C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.828

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]

ACMG classification

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
RMI1	NM_001358291.2	c.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
RMI1	ENST00000445877.6	c.71C>T	p.Pro24Leu	missense_variant	Exon 3 of 3	1	NM_001358291.2	ENSP00000402433.2
RMI1	ENST00000325875.7	c.71C>T	p.Pro24Leu	missense_variant	Exon 3 of 3	2		ENSP00000317039.3

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152064 Hom.: 1 Cov.: 32

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

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

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

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

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

Other links and lift over

dbSNP: rs373651916; hg19: chr9-86615972;