NM_017909.4:c.1317+57dupG

Variant names:

• chr6-151405662-G-GC
• rs149556269
• NM_017909.4:c.1317+57dupG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017909.4(RMND1):​c.1317+57dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 685,286 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: RMND1 NM_017909.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• Publications: 1 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.1317+57dupG		intron	N/A	NP_060379.2	Q9NWS8-1
	RMND1	NM_001271937.2		c.807+57dupG		intron	N/A	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.1317+57_1317+58insG		intron	N/A	ENSP00000412708.2	Q9NWS8-1
	RMND1	ENST00000682641.1		c.1317+57_1317+58insG		intron	N/A	ENSP00000506793.1	A0A804HHW6
	RMND1	ENST00000949374.1		c.1341+57_1341+58insG		intron	N/A	ENSP00000619433.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000146 AC: 1 AN: 685286 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 365610

African (AFR) AF: 0.00 AC: 0 AN: 17840

American (AMR) AF: 0.00 AC: 0 AN: 35458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19346

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35712

South Asian (SAS) AF: 0.00 AC: 0 AN: 64230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3964

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 425244

Other (OTH) AF: 0.00 AC: 0 AN: 34436

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.48

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: rs149556269; hg19: chr6-151726797;