9-84001596-G-C

Variant names:

• chr9-84001596-G-C
• NM_001358291.2:c.610G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001358291.2(RMI1):​c.610G>C​(p.Glu204Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RMI1 NM_001358291.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.90

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18309152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMI1	NM_001358291.2	c.610G>C	p.Glu204Gln	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.610G>C	p.Glu204Gln	missense_variant	Exon 3 of 3	1	NM_001358291.2	ENSP00000402433.2
RMI1	ENST00000325875.7	c.610G>C	p.Glu204Gln	missense_variant	Exon 3 of 3	2		ENSP00000317039.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 01, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.610G>C (p.E204Q) alteration is located in exon 3 (coding exon 1) of the RMI1 gene. This alteration results from a G to C substitution at nucleotide position 610, causing the glutamic acid (E) at amino acid position 204 to be replaced by a glutamine (Q). 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	0.18
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T;T
Eigen	Benign	-0.0022
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.079
Sift	Benign	0.048	D;T
Sift4G	Benign	0.22	T;T
Polyphen		0.038	.;B
Vest4		0.14
MutPred		0.29		Gain of methylation at K205 (P = 0.0988);Gain of methylation at K205 (P = 0.0988);
MVP		0.55
MPC		0.073
ClinPred		0.44	T
GERP RS		5.6
Varity_R		0.24
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-86616511;