chr6-151405662-GC-G

Position:

• chr6-151405662-GC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_017909.4(RMND1):​c.1317+57del 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RMND1	NM_017909.4	c.1317+57del		intron_variant		ENST00000444024.3
RMND1	NM_001271937.2	c.807+57del		intron_variant
RMND1	XM_047418959.1	c.1317+57del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RMND1	ENST00000444024.3	c.1317+57del		intron_variant		3	NM_017909.4	P1

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

Gnomad4 AFR exome AF: 0.00533

Gnomad4 AMR exome AF: 0.0186

Gnomad4 ASJ exome AF: 0.00744

Gnomad4 EAS exome AF: 0.000196

Gnomad4 SAS exome AF: 0.0265

Gnomad4 FIN exome AF: 0.0339

Gnomad4 NFE exome AF: 0.0327

Gnomad4 OTH exome AF: 0.0266

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

Gnomad4 AFR AF: 0.00626

Gnomad4 AMR AF: 0.0193

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0235

Gnomad4 FIN AF: 0.0356

Gnomad4 NFE AF: 0.0339

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0232 Hom.: 4

Bravo AF: 0.0204

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs149556269; hg19: chr6-151726797;