rs768068417

Variant names:

• chr9-84001512-C-A
• NM_001358291.2:c.526C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-84001512-C-A
• chr9-84001512-C-T

Variant summary

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

The NM_001358291.2(RMI1):​c.526C>A​(p.Arg176Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,572 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R176C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RMI1 NM_001358291.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMI1	NM_001358291.2	c.526C>A	p.Arg176Ser	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.526C>A	p.Arg176Ser	missense_variant	Exon 3 of 3	1	NM_001358291.2	ENSP00000402433.2
RMI1	ENST00000325875.7	c.526C>A	p.Arg176Ser	missense_variant	Exon 3 of 3	2		ENSP00000317039.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461572 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727078

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.061
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Benign	0.28
Sift	Benign	0.040	D;D
Sift4G	Uncertain	0.035	D;D
Polyphen		0.25	.;B
Vest4		0.44
MutPred		0.63		Loss of methylation at R176 (P = 0.0604);Loss of methylation at R176 (P = 0.0604);
MVP		0.58
MPC		0.19
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.94
gMVP		0.85

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: chr9-86616427;