6-151405662-GCC-GC

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_017909.4(RMND1):​c.1317+57delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 837,288 control chromosomes in the GnomAD database, including 394 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (45 hom., cov: 32)
  • Exomes 𝑓: 0.028 (349 hom.)
• Consequence: RMND1 NM_017909.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-151405662-GC-G is Benign according to our data. Variant chr6-151405662-GC-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1185959.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0226 (3441/152176) while in subpopulation NFE AF = 0.0339 (2303/68014). AF 95% confidence interval is 0.0327. There are 45 homozygotes in GnomAd4. There are 1642 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 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+57delG		intron	N/A	NP_060379.2	Q9NWS8-1
	RMND1	NM_001271937.2		c.807+57delG		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+57delG		intron	N/A	ENSP00000412708.2	Q9NWS8-1
	RMND1	ENST00000682641.1		c.1317+57delG		intron	N/A	ENSP00000506793.1	A0A804HHW6
	RMND1	ENST00000949374.1		c.1341+57delG		intron	N/A	ENSP00000619433.1

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3445 AN: 152058 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.00628

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0193

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0237

Gnomad FIN AF: 0.0356

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0339

Gnomad OTH AF: 0.0253

GnomAD4 exome AF: 0.0280 AC: 19177 AN: 685112 Hom.: 349 AF XY: 0.0282 AC XY: 10322 AN XY: 365520

African (AFR) AF: 0.00533 AC: 95 AN: 17840

American (AMR) AF: 0.0186 AC: 659 AN: 35454

Ashkenazi Jewish (ASJ) AF: 0.00744 AC: 144 AN: 19344

East Asian (EAS) AF: 0.000196 AC: 7 AN: 35712

South Asian (SAS) AF: 0.0265 AC: 1701 AN: 64214

European-Finnish (FIN) AF: 0.0339 AC: 1663 AN: 49042

Middle Eastern (MID) AF: 0.0247 AC: 98 AN: 3964

European-Non Finnish (NFE) AF: 0.0327 AC: 13893 AN: 425112

Other (OTH) AF: 0.0266 AC: 917 AN: 34430

GnomAD4 genome AF: 0.0226 AC: 3441 AN: 152176 Hom.: 45 Cov.: 32 AF XY: 0.0221 AC XY: 1642 AN XY: 74412

African (AFR) AF: 0.00626 AC: 260 AN: 41512

American (AMR) AF: 0.0193 AC: 295 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00864 AC: 30 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0235 AC: 113 AN: 4816

European-Finnish (FIN) AF: 0.0356 AC: 376 AN: 10570

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0339 AC: 2303 AN: 68014

Other (OTH) AF: 0.0246 AC: 52 AN: 2116

Alfa AF: 0.0232 Hom.: 4

Bravo AF: 0.0204

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

ClinVar submissions as Germline

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
PhyloP100		0.48
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: rs149556269; hg19: chr6-151726797;