9-84002350-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001358291.2(RMI1):​c.1364A>T​(p.Asn455Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N455S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RMI1 NM_001358291.2 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03968984).

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>T	p.Asn455Ile	missense	Exon 3 of 3	NP_001345220.1	Q9H9A7
	RMI1	NM_001358292.2		c.1364A>T	p.Asn455Ile	missense	Exon 4 of 4	NP_001345221.1	Q9H9A7
	RMI1	NM_001358293.2		c.1364A>T	p.Asn455Ile	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>T	p.Asn455Ile	missense	Exon 3 of 3	ENSP00000402433.2	Q9H9A7
	RMI1	ENST00000325875.7	TSL:2	c.1364A>T	p.Asn455Ile	missense	Exon 3 of 3	ENSP00000317039.3	Q9H9A7
	RMI1	ENST00000891301.1		c.1364A>T	p.Asn455Ile	missense	Exon 3 of 3	ENSP00000561360.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 155405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.6
DANN	Benign	0.54
DEOGEN2	Benign	0.046	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.35
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.0070
Sift	Uncertain	0.010	D
Sift4G	Benign	0.18	T
Polyphen		0.0050	B
Vest4		0.080
MutPred		0.18		Loss of ubiquitination at K453 (P = 0.0539)
MVP		0.16
MPC		0.090
ClinPred		0.054	T
GERP RS		-3.0
Varity_R		0.089
gMVP		0.25
Mutation Taster		=97/3	polymorphism

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;