rs771894262

chr6-151433213-C-Gchr6-151433213-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_017909.4(RMND1):c.631G>C(p.Val211Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V211M) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RMND1 NM_017909.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.24

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr6-151433213-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 225260.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.1840764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RMND1	NM_017909.4	c.631G>C	p.Val211Leu	missense_variant	4/12	ENST00000444024.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RMND1	ENST00000444024.3	c.631G>C	p.Val211Leu	missense_variant	4/12	3	NM_017909.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249916 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135100

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0060	T;T;T
Eigen	Benign	0.013
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.60	T
REVEL	Benign	0.032
Polyphen		0.23	B;B;.
Vest4		0.41, 0.44
MutPred		0.31		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;
MVP		0.20
MPC		0.49
ClinPred		0.72	D
GERP RS		5.2
Varity_R		0.21
gMVP		0.64

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: rs771894262; hg19: chr6-151754348;