NM_017909.4:c.*195C>A

Variant names:

• chr6-151405040-G-T
• rs3757312
• NM_017909.4:c.*195C>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.*195C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 499,788 control chromosomes in the GnomAD database, including 28,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (12556 hom., cov: 31)
  • Exomes 𝑓: 0.28 (16223 hom.)
• Consequence: RMND1 NM_017909.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.385
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-151405040-G-T is Benign according to our data. Variant chr6-151405040-G-T is described in ClinVar as Benign. ClinVar VariationId is 1241989.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 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.*195C>A		3_prime_UTR	Exon 12 of 12	NP_060379.2	Q9NWS8-1
	RMND1	NM_001271937.2		c.*195C>A		3_prime_UTR	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.*195C>A		3_prime_UTR	Exon 12 of 12	ENSP00000412708.2	Q9NWS8-1
	RMND1	ENST00000949374.1		c.*195C>A		3_prime_UTR	Exon 12 of 12	ENSP00000619433.1
	RMND1	ENST00000683724.1		c.*195C>A		3_prime_UTR	Exon 12 of 12	ENSP00000507984.1	Q9NWS8-1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56133 AN: 151662 Hom.: 12530 Cov.: 31

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.280 AC: 97325 AN: 348008 Hom.: 16223 Cov.: 3 AF XY: 0.283 AC XY: 52317 AN XY: 184812

African (AFR) AF: 0.589 AC: 4546 AN: 7724

American (AMR) AF: 0.353 AC: 3638 AN: 10300

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 2994 AN: 10420

East Asian (EAS) AF: 0.575 AC: 12085 AN: 21020

South Asian (SAS) AF: 0.371 AC: 13679 AN: 36898

European-Finnish (FIN) AF: 0.240 AC: 6157 AN: 25604

Middle Eastern (MID) AF: 0.293 AC: 456 AN: 1554

European-Non Finnish (NFE) AF: 0.223 AC: 47759 AN: 214338

Other (OTH) AF: 0.298 AC: 6011 AN: 20150

GnomAD4 genome AF: 0.370 AC: 56212 AN: 151780 Hom.: 12556 Cov.: 31 AF XY: 0.373 AC XY: 27696 AN XY: 74166

African (AFR) AF: 0.602 AC: 24911 AN: 41368

American (AMR) AF: 0.352 AC: 5372 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1042 AN: 3468

East Asian (EAS) AF: 0.682 AC: 3493 AN: 5122

South Asian (SAS) AF: 0.380 AC: 1835 AN: 4824

European-Finnish (FIN) AF: 0.253 AC: 2663 AN: 10544

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

European-Non Finnish (NFE) AF: 0.232 AC: 15785 AN: 67902

Other (OTH) AF: 0.357 AC: 752 AN: 2106

Alfa AF: 0.303 Hom.: 1091

Bravo AF: 0.390

Asia WGS AF: 0.533 AC: 1850 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.93
CADD	Benign	0.52
DANN	Benign	0.68
PhyloP100		-0.39
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: rs3757312; hg19: chr6-151726175;