rs955458468

Variant names:

• chr1-151760163-C-G
• rs955458468
• NM_031420.4:c.691G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-151760163-C-G
• chr1-151760163-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031420.4(MRPL9):​c.691G>C​(p.Val231Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MRPL9 NM_031420.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06
• Publications: 0 publications found

Genes affected

MRPL9 (HGNC:14277): (mitochondrial ribosomal protein L9) This is a nuclear gene encoding a protein component of the 39S subunit of the mitochondrial ribosome. Alternative splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 8. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16850969).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031420.4. 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
	MRPL9	NM_031420.4	MANE Select	c.691G>C	p.Val231Leu	missense	Exon 7 of 7	NP_113608.1	Q9BYD2
	MRPL9	NM_001300733.2		c.589G>C	p.Val197Leu	missense	Exon 6 of 6	NP_001287662.1	Q5SZR1
	MRPL9	NR_125331.2		n.748G>C		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL9	ENST00000368830.8	TSL:1 MANE Select	c.691G>C	p.Val231Leu	missense	Exon 7 of 7	ENSP00000357823.3	Q9BYD2
	MRPL9	ENST00000368829.3	TSL:2	c.589G>C	p.Val197Leu	missense	Exon 6 of 6	ENSP00000357822.3	Q5SZR1
	MRPL9	ENST00000467306.5	TSL:2	n.*362G>C		non_coding_transcript_exon	Exon 7 of 7	ENSP00000492374.1	A0A1W2PRK9

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000957

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461840 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111982

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.000393 AC: 6 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68048

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000132

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.1
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.20
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.022	D
Polyphen		0.24	B
Vest4		0.41
MutPred		0.60		Loss of catalytic residue at V231 (P = 0.0665)
MVP		0.21
MPC		0.72
ClinPred		0.69	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.78
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs955458468; hg19: chr1-151732639;