6-151445672-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017909.4(RMND1):c.140G>A(p.Arg47His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,614,092 control chromosomes in the GnomAD database, including 38 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 (★★).

Frequency

Genomes: 𝑓 0.0084 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 19 hom. )

Consequence

RMND1
NM_017909.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.23

Publications

6 publications found

Variant links:

Genes affected

RMND1 (HGNC:21176): (required for meiotic nuclear division 1 homolog) The protein encoded by this gene belongs to the evolutionary conserved sif2 family of proteins that share the DUF155 domain in common. This protein is thought to be localized in the mitochondria and involved in mitochondrial translation. Mutations in this gene are associated with combined oxidative phosphorylation deficiency-11. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

RMND1 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
combined oxidative phosphorylation defect type 11
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics

RMND1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025806427).

BP6

Variant 6-151445672-C-T is Benign according to our data. Variant chr6-151445672-C-T is described in ClinVar as Benign. ClinVar VariationId is 377296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00836 (1273/152232) while in subpopulation AFR AF = 0.0286 (1187/41532). AF 95% confidence interval is 0.0272. There are 19 homozygotes in GnomAd4. There are 603 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017909.4. 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
	RMND1	NM_017909.4	MANE Select	c.140G>A	p.Arg47His	missense	Exon 2 of 12	NP_060379.2	Q9NWS8-1
	RMND1	NM_001271937.2		c.-7+6344G>A		intron	N/A	NP_001258866.1	A0A087WXU0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RMND1	ENST00000444024.3	TSL:3 MANE Select	c.140G>A	p.Arg47His	missense	Exon 2 of 12	ENSP00000412708.2	Q9NWS8-1
RMND1	ENST00000491268.2	TSL:1	c.140G>A	p.Arg47His	missense	Exon 2 of 3	ENSP00000494948.1	Q9NWS8-3
RMND1	ENST00000682641.1		c.140G>A	p.Arg47His	missense	Exon 2 of 12	ENSP00000506793.1	A0A804HHW6

Frequencies

GnomAD3 genomes

AF:

0.00830

AC:

1262

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0284

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00245

AC:

617

AN:

251478

AF XY:

0.00196

show subpopulations

Gnomad AFR exome

AF:

0.0284

Gnomad AMR exome

AF:

0.00269

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000440

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00114

AC:

1671

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

735

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0303

AC:

1013

AN:

33478

American (AMR)

AF:

0.00271

AC:

121

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00329

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000331

AC:

368

AN:

1111996

Other (OTH)

AF:

0.00230

AC:

139

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

104

208

312

416

520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00836

AC:

1273

AN:

152232

Hom.:

Cov.:

AF XY:

0.00810

AC XY:

603

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0286

AC:

1187

AN:

41532

American (AMR)

AF:

0.00288

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68014

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

116

175

233

291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00674

Hom.:

Bravo

AF:

0.00926

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0259

AC:

114

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00286

AC:

347

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000533

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.42

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0021

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

-1.2

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.51

REVEL

Benign

0.032

Sift

Benign

0.14

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.050

MVP

0.055

MPC

0.26

ClinPred

0.0013

GERP RS

-6.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.013

gMVP

0.11

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over