rs35819647

Variant names:

• chr9-84001041-C-T
• rs35819647
• NM_001358291.2:c.55C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-84001041-C-T
• chr9-84001041-C-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001358291.2(RMI1):​c.55C>T​(p.His19Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000797 in 1,613,600 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (1 hom.)
• Consequence: RMI1 NM_001358291.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.98
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011101633).
• BP6: Variant 9-84001041-C-T is Benign according to our data. Variant chr9-84001041-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2659283.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.55C>T	p.His19Tyr	missense	Exon 3 of 3	NP_001345220.1	Q9H9A7
	RMI1	NM_001358292.2		c.55C>T	p.His19Tyr	missense	Exon 4 of 4	NP_001345221.1	Q9H9A7
	RMI1	NM_001358293.2		c.55C>T	p.His19Tyr	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.55C>T	p.His19Tyr	missense	Exon 3 of 3	ENSP00000402433.2	Q9H9A7
	RMI1	ENST00000325875.7	TSL:2	c.55C>T	p.His19Tyr	missense	Exon 3 of 3	ENSP00000317039.3	Q9H9A7
	RMI1	ENST00000891301.1		c.55C>T	p.His19Tyr	missense	Exon 3 of 3	ENSP00000561360.1

Frequencies

GnomAD3 genomes AF: 0.00265 AC: 403 AN: 152104 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00780

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.000945 AC: 237 AN: 250706 AF XY: 0.000856

Gnomad AFR exome AF: 0.00722

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.000897

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000926

Gnomad NFE exome AF: 0.000432

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.000603 AC: 881 AN: 1461378 Hom.: 1 Cov.: 32 AF XY: 0.000622 AC XY: 452 AN XY: 727006

African (AFR) AF: 0.00855 AC: 286 AN: 33452

American (AMR) AF: 0.00172 AC: 77 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.000613 AC: 16 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86222

European-Finnish (FIN) AF: 0.000281 AC: 15 AN: 53384

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5766

European-Non Finnish (NFE) AF: 0.000334 AC: 371 AN: 1111764

Other (OTH) AF: 0.00157 AC: 95 AN: 60366

GnomAD4 genome AF: 0.00266 AC: 405 AN: 152222 Hom.: 3 Cov.: 32 AF XY: 0.00250 AC XY: 186 AN XY: 74420

African (AFR) AF: 0.00782 AC: 325 AN: 41546

American (AMR) AF: 0.00222 AC: 34 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 68012

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00112 Hom.: 2

Bravo AF: 0.00288

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00772 AC: 34

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00107 AC: 130

EpiCase AF: 0.000491

EpiControl AF: 0.000830

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.0
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.33
Sift	Benign	0.057	T
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.53
MVP		0.66
MPC		0.45
ClinPred		0.036	T
GERP RS		5.0
Varity_R		0.54
gMVP		0.84
Mutation Taster		=83/17	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: rs35819647; hg19: chr9-86615956;