Genetic Variant RMND1:c.1317+99A>G (chr6-151405621-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_017909.4(RMND1):c.1317+99A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 680,652 control chromosomes in the GnomAD database, including 38,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 12429 hom., cov: 32)

Exomes 𝑓: 0.29 ( 25918 hom. )

Consequence

RMND1
NM_017909.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.825

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-151405621-T-C is Benign according to our data. Variant chr6-151405621-T-C is described in ClinVar as [Benign]. Clinvar id is 1291373.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMND1	NM_017909.4 link	c.1317+99A>G		intron_variant	Intron 11 of 11	ENST00000444024.3	NP_060379.2	Q9NWS8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMND1	ENST00000444024.3 link	c.1317+99A>G		intron_variant	Intron 11 of 11	3	NM_017909.4	ENSP00000412708.2		Q9NWS8-1

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55992

AN:

151990

Hom.:

12403

Cov.:

show subpopulations

Gnomad AFR

AF:

0.596

Gnomad AMI

AF:

0.299

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.681

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.349

GnomAD4 exome

AF:

0.290

AC:

153019

AN:

528544

Hom.:

25918

AF XY:

0.290

AC XY:

81591

AN XY:

281556

show subpopulations

Gnomad4 AFR exome

AF:

0.599

AC:

8428

AN:

14076

Gnomad4 AMR exome

AF:

0.358

AC:

8695

AN:

24258

Gnomad4 ASJ exome

AF:

0.299

AC:

4417

AN:

14754

Gnomad4 EAS exome

AF:

0.600

AC:

20185

AN:

33662

Gnomad4 SAS exome

AF:

0.371

AC:

17373

AN:

46884

Gnomad4 FIN exome

AF:

0.247

AC:

9684

AN:

39252

Gnomad4 NFE exome

AF:

0.230

AC:

74715

AN:

324294

Gnomad4 Remaining exome

AF:

0.304

AC:

8719

AN:

28648

Heterozygous variant carriers

4835

9670

14504

19339

24174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

1036

2072

3108

4144

5180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.369

AC:

56070

AN:

152108

Hom.:

12429

Cov.:

AF XY:

0.371

AC XY:

27625

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.596

AC:

0.596252

AN:

0.596252

Gnomad4 AMR

AF:

0.352

AC:

0.351682

AN:

0.351682

Gnomad4 ASJ

AF:

0.300

AC:

0.300461

AN:

0.300461

Gnomad4 EAS

AF:

0.680

AC:

0.679977

AN:

0.679977

Gnomad4 SAS

AF:

0.380

AC:

0.380133

AN:

0.380133

Gnomad4 FIN

AF:

0.252

AC:

0.252171

AN:

0.252171

Gnomad4 NFE

AF:

0.232

AC:

0.232298

AN:

0.232298

Gnomad4 OTH

AF:

0.356

AC:

0.355924

AN:

0.355924

Heterozygous variant carriers

1643

3285

4928

6570

8213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.311

Hom.:

1355

Bravo

AF:

0.389

Asia WGS

AF:

0.532

AC:

1847

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.28

DANN

Benign

0.80

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over