6-151405264-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017909.4(RMND1):c.1321A>C(p.Met441Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000432 in 1,612,596 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 3 hom. )

Consequence

RMND1
NM_017909.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.52

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009570837).

BP6

Variant 6-151405264-T-G is Benign according to our data. Variant chr6-151405264-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1215831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000421 (615/1460308) while in subpopulation NFE AF= 0.000257 (286/1110706). AF 95% confidence interval is 0.000233. There are 3 homozygotes in gnomad4_exome. There are 283 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMND1	NM_017909.4 link	c.1321A>C	p.Met441Leu	missense_variant	Exon 12 of 12	ENST00000444024.3	NP_060379.2	Q9NWS8-1
RMND1	NM_001271937.2 link	c.811A>C	p.Met271Leu	missense_variant	Exon 11 of 11		NP_001258866.1	Q9NWS8A0A087WXU0
RMND1	XM_047418959.1 link	c.1321A>C	p.Met441Leu	missense_variant	Exon 12 of 13		XP_047274915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMND1	ENST00000444024.3 link	c.1321A>C	p.Met441Leu	missense_variant	Exon 12 of 12	3	NM_017909.4	ENSP00000412708.2		Q9NWS8-1

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00613

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000757

AC:

190

AN:

250926

Hom.:

AF XY:

0.000678

AC XY:

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00527

Gnomad NFE exome

AF:

0.000670

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000421

AC:

615

AN:

1460308

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

283

AN XY:

726582

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

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:

0.00556

Gnomad4 NFE exome

AF:

0.000257

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.000538

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00613

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000273

Hom.:

Bravo

AF:

0.000125

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000914

AC:

111

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 09, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0055

T;T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.73

.;T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.0096

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N;.

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.99

.;N;.

REVEL

Benign

0.13

Sift

Benign

0.53

.;T;.

Sift4G

Benign

0.61

.;T;T

Polyphen

0.0

B;B;.

Vest4

0.21, 0.21

MutPred

0.38

Gain of catalytic residue at M441 (P = 0.0155);Gain of catalytic residue at M441 (P = 0.0155);.;

MVP

0.28

MPC

0.20

ClinPred

0.018

GERP RS

3.8

Varity_R

0.14

gMVP

0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over