chr6-151405248-C-A

Variant names:

• chr6-151405248-C-A
• NM_017909.4:c.1337G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017909.4(RMND1):​c.1337G>T​(p.Arg446Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,538 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RMND1 NM_017909.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMND1	NM_017909.4	c.1337G>T	p.Arg446Leu	missense_variant	Exon 12 of 12	ENST00000444024.3	NP_060379.2
RMND1	NM_001271937.2	c.827G>T	p.Arg276Leu	missense_variant	Exon 11 of 11		NP_001258866.1
RMND1	XM_047418959.1	c.1337G>T	p.Arg446Leu	missense_variant	Exon 12 of 13		XP_047274915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMND1	ENST00000444024.3	c.1337G>T	p.Arg446Leu	missense_variant	Exon 12 of 12	3	NM_017909.4	ENSP00000412708.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460538 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726686

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T;T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	.;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.50	D;D;D
MetaSVM	Uncertain	-0.079	T
MutationAssessor	Uncertain	2.4	M;M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.6	.;N;.
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	.;D;.
Sift4G	Uncertain	0.0090	.;D;D
Polyphen		1.0	D;D;.
Vest4		0.82, 0.68
MutPred		0.46		Loss of disorder (P = 0.0107);Loss of disorder (P = 0.0107);.;
MVP		0.67
MPC		0.89
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.19
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.32		Position offset: 19

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-151726383;