NM_017909.4:c.1317+96C>G

Variant names:

• chr6-151405624-G-C
• rs144734502
• NM_017909.4:c.1317+96C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017909.4(RMND1):​c.1317+96C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 683,916 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (1 hom.)
• Consequence: RMND1 NM_017909.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.338
• Publications: 0 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=-0.85).
• BP6: Variant 6-151405624-G-C is Benign according to our data. Variant chr6-151405624-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1187784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00554 (844/152270) while in subpopulation AFR AF = 0.0191 (794/41548). AF 95% confidence interval is 0.018. There are 6 homozygotes in GnomAd4. There are 394 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

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+96C>G		intron	N/A	NP_060379.2	Q9NWS8-1
	RMND1	NM_001271937.2		c.807+96C>G		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+96C>G		intron	N/A	ENSP00000412708.2	Q9NWS8-1
	RMND1	ENST00000682641.1		c.1317+96C>G		intron	N/A	ENSP00000506793.1	A0A804HHW6
	RMND1	ENST00000949374.1		c.1341+96C>G		intron	N/A	ENSP00000619433.1

Frequencies

GnomAD3 genomes AF: 0.00555 AC: 845 AN: 152152 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.000683 AC: 363 AN: 531646 Hom.: 1 AF XY: 0.000572 AC XY: 162 AN XY: 283316

African (AFR) AF: 0.0211 AC: 296 AN: 14040

American (AMR) AF: 0.00106 AC: 26 AN: 24510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14832

East Asian (EAS) AF: 0.00 AC: 0 AN: 33592

South Asian (SAS) AF: 0.0000426 AC: 2 AN: 46950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2802

European-Non Finnish (NFE) AF: 0.0000153 AC: 5 AN: 326404

Other (OTH) AF: 0.00119 AC: 34 AN: 28658

GnomAD4 genome AF: 0.00554 AC: 844 AN: 152270 Hom.: 6 Cov.: 33 AF XY: 0.00529 AC XY: 394 AN XY: 74474

African (AFR) AF: 0.0191 AC: 794 AN: 41548

American (AMR) AF: 0.00235 AC: 36 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68014

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00430 Hom.: 2

Bravo AF: 0.00640

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.85
CADD	Benign	0.82
DANN	Benign	0.75
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism

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: rs144734502; hg19: chr6-151726759;