NM_017909.4:c.1317+26G>A

Variant names:

• chr6-151405694-C-T
• rs3757315
• NM_017909.4:c.1317+26G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017909.4(RMND1):​c.1317+26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,091,798 control chromosomes in the GnomAD database, including 55,637 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (12953 hom., cov: 32)
  • Exomes 𝑓: 0.28 (42684 hom.)
• Consequence: RMND1 NM_017909.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.535
• 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-151405694-C-T is Benign according to our data. Variant chr6-151405694-C-T is described in ClinVar as Benign. ClinVar VariationId is 1223720.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 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.1317+26G>A		intron	N/A	NP_060379.2	Q9NWS8-1
	RMND1	NM_001271937.2		c.807+26G>A		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+26G>A		intron	N/A	ENSP00000412708.2	Q9NWS8-1
	RMND1	ENST00000682641.1		c.1317+26G>A		intron	N/A	ENSP00000506793.1	A0A804HHW6
	RMND1	ENST00000949374.1		c.1341+26G>A		intron	N/A	ENSP00000619433.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56823 AN: 151876 Hom.: 12923 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.355

GnomAD2 exomes AF: 0.332 AC: 81431 AN: 244956 AF XY: 0.325

Gnomad AFR exome AF: 0.620

Gnomad AMR exome AF: 0.354

Gnomad ASJ exome AF: 0.293

Gnomad EAS exome AF: 0.707

Gnomad FIN exome AF: 0.253

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.294

GnomAD4 exome AF: 0.279 AC: 262434 AN: 939804 Hom.: 42684 Cov.: 12 AF XY: 0.280 AC XY: 137103 AN XY: 489266

African (AFR) AF: 0.623 AC: 14444 AN: 23190

American (AMR) AF: 0.359 AC: 15234 AN: 42380

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 6724 AN: 22728

East Asian (EAS) AF: 0.615 AC: 22888 AN: 37230

South Asian (SAS) AF: 0.375 AC: 27960 AN: 74578

European-Finnish (FIN) AF: 0.251 AC: 13080 AN: 52196

Middle Eastern (MID) AF: 0.306 AC: 1433 AN: 4684

European-Non Finnish (NFE) AF: 0.230 AC: 147311 AN: 639746

Other (OTH) AF: 0.310 AC: 13360 AN: 43072

GnomAD4 genome AF: 0.374 AC: 56908 AN: 151994 Hom.: 12953 Cov.: 32 AF XY: 0.378 AC XY: 28058 AN XY: 74288

African (AFR) AF: 0.614 AC: 25465 AN: 41452

American (AMR) AF: 0.353 AC: 5394 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1042 AN: 3470

East Asian (EAS) AF: 0.691 AC: 3563 AN: 5154

South Asian (SAS) AF: 0.381 AC: 1833 AN: 4812

European-Finnish (FIN) AF: 0.253 AC: 2667 AN: 10562

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15820 AN: 67966

Other (OTH) AF: 0.363 AC: 767 AN: 2112

Alfa AF: 0.278 Hom.: 19532

Bravo AF: 0.395

Asia WGS AF: 0.551 AC: 1912 AN: 3478

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.12
DANN	Benign	0.41
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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: rs3757315; hg19: chr6-151726829; COSMIC: COSV60549969; COSMIC: COSV60549969;