9-84002350-A-G

Variant names:

• chr9-84002350-A-G
• rs1982151
• NM_001358291.2:c.1364A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001358291.2(RMI1):​c.1364A>G​(p.Asn455Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 1,603,676 control chromosomes in the GnomAD database, including 425,676 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 Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.69 (37123 hom., cov: 32)
  • Exomes 𝑓: 0.73 (388553 hom.)
• Consequence: RMI1 NM_001358291.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.353
• Publications: 75 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2284054E-6).
• BP6: Variant 9-84002350-A-G is Benign according to our data. Variant chr9-84002350-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060293.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358291.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMI1	NM_001358291.2	MANE Select	c.1364A>G	p.Asn455Ser	missense	Exon 3 of 3	NP_001345220.1	Q9H9A7
	RMI1	NM_001358292.2		c.1364A>G	p.Asn455Ser	missense	Exon 4 of 4	NP_001345221.1	Q9H9A7
	RMI1	NM_001358293.2		c.1364A>G	p.Asn455Ser	missense	Exon 4 of 4	NP_001345222.1	Q9H9A7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMI1	ENST00000445877.6	TSL:1 MANE Select	c.1364A>G	p.Asn455Ser	missense	Exon 3 of 3	ENSP00000402433.2	Q9H9A7
	RMI1	ENST00000325875.7	TSL:2	c.1364A>G	p.Asn455Ser	missense	Exon 3 of 3	ENSP00000317039.3	Q9H9A7
	RMI1	ENST00000891301.1		c.1364A>G	p.Asn455Ser	missense	Exon 3 of 3	ENSP00000561360.1

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105554 AN: 151940 Hom.: 37100 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.691

GnomAD2 exomes AF: 0.726 AC: 178742 AN: 246318 AF XY: 0.717

Gnomad AFR exome AF: 0.584

Gnomad AMR exome AF: 0.855

Gnomad ASJ exome AF: 0.719

Gnomad EAS exome AF: 0.735

Gnomad FIN exome AF: 0.744

Gnomad NFE exome AF: 0.729

Gnomad OTH exome AF: 0.732

GnomAD4 exome AF: 0.730 AC: 1059489 AN: 1451618 Hom.: 388553 Cov.: 37 AF XY: 0.726 AC XY: 524738 AN XY: 722812

African (AFR) AF: 0.577 AC: 19099 AN: 33080

American (AMR) AF: 0.848 AC: 37449 AN: 44176

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 18644 AN: 25952

East Asian (EAS) AF: 0.734 AC: 29043 AN: 39580

South Asian (SAS) AF: 0.618 AC: 53116 AN: 85912

European-Finnish (FIN) AF: 0.742 AC: 39471 AN: 53198

Middle Eastern (MID) AF: 0.666 AC: 3818 AN: 5730

European-Non Finnish (NFE) AF: 0.739 AC: 815947 AN: 1104046

Other (OTH) AF: 0.716 AC: 42902 AN: 59944

GnomAD4 genome AF: 0.695 AC: 105632 AN: 152058 Hom.: 37123 Cov.: 32 AF XY: 0.693 AC XY: 51549 AN XY: 74340

African (AFR) AF: 0.581 AC: 24080 AN: 41458

American (AMR) AF: 0.784 AC: 11982 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2505 AN: 3470

East Asian (EAS) AF: 0.732 AC: 3792 AN: 5180

South Asian (SAS) AF: 0.635 AC: 3065 AN: 4828

European-Finnish (FIN) AF: 0.744 AC: 7865 AN: 10574

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.735 AC: 49942 AN: 67956

Other (OTH) AF: 0.687 AC: 1450 AN: 2110

Alfa AF: 0.720 Hom.: 155405

Bravo AF: 0.697

TwinsUK AF: 0.740 AC: 2743

ALSPAC AF: 0.749 AC: 2886

ESP6500AA AF: 0.586 AC: 2571

ESP6500EA AF: 0.737 AC: 6321

ExAC AF: 0.712 AC: 86353

Asia WGS AF: 0.686 AC: 2385 AN: 3476

EpiCase AF: 0.733

EpiControl AF: 0.727

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	RMI1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.97	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.21
DANN	Benign	0.096
DEOGEN2	Benign	0.028	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0073	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.35
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.96	N
REVEL	Benign	0.012
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0080
MPC		0.059
ClinPred		0.0010	T
GERP RS		-3.0
Varity_R		0.017
gMVP		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1982151; hg19: chr9-86617265; COSMIC: COSV107353594; COSMIC: COSV107353594;