6-151405236-C-T

Variant names:

• chr6-151405236-C-T
• rs115079861
• NM_017909.4:c.1349G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_017909.4(RMND1):​c.1349G>A​(p.Ter450Ter) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,612,096 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (58 hom.)
• Consequence: RMND1 NM_017909.4 stop_retained
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00900
• Publications: 10 publications found

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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 6-151405236-C-T is Benign according to our data. Variant chr6-151405236-C-T is described in ClinVar as Benign. ClinVar VariationId is 138915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.009 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0539 is higher than 0.05.

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.1349G>A	p.Ter450Ter	stop_retained	Exon 12 of 12	NP_060379.2	Q9NWS8-1
	RMND1	NM_001271937.2		c.839G>A	p.Ter280Ter	stop_retained	Exon 11 of 11	NP_001258866.1	A0A087WXU0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMND1	ENST00000444024.3	TSL:3 MANE Select	c.1349G>A	p.Ter450Ter	stop_retained	Exon 12 of 12	ENSP00000412708.2	Q9NWS8-1
	RMND1	ENST00000949374.1		c.1373G>A	p.Ter458Ter	stop_retained	Exon 12 of 12	ENSP00000619433.1
	RMND1	ENST00000683724.1		c.1349G>A	p.Ter450Ter	stop_retained	Exon 12 of 12	ENSP00000507984.1	Q9NWS8-1

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2422 AN: 152102 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00865

GnomAD2 exomes AF: 0.00397 AC: 997 AN: 250924 AF XY: 0.00292

Gnomad AFR exome AF: 0.0546

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00155 AC: 2269 AN: 1459876 Hom.: 58 Cov.: 29 AF XY: 0.00135 AC XY: 984 AN XY: 726418

African (AFR) AF: 0.0561 AC: 1869 AN: 33332

American (AMR) AF: 0.00255 AC: 114 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86164

European-Finnish (FIN) AF: 0.000805 AC: 43 AN: 53408

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5764

European-Non Finnish (NFE) AF: 0.0000531 AC: 59 AN: 1110464

Other (OTH) AF: 0.00274 AC: 165 AN: 60324

GnomAD4 genome AF: 0.0159 AC: 2421 AN: 152220 Hom.: 60 Cov.: 32 AF XY: 0.0149 AC XY: 1108 AN XY: 74446

African (AFR) AF: 0.0558 AC: 2317 AN: 41530

American (AMR) AF: 0.00445 AC: 68 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000566 AC: 6 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68010

Other (OTH) AF: 0.00856 AC: 18 AN: 2104

Alfa AF: 0.00577 Hom.: 13

Bravo AF: 0.0186

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.5
DANN	Benign	0.75
PhyloP100		-0.0090
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs115079861; hg19: chr6-151726371;