NM_031420.4:c.604G>A

Variant names:

• chr1-151760884-C-T
• NM_031420.4:c.604G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031420.4(MRPL9):​c.604G>A​(p.Ala202Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,320,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: MRPL9 NM_031420.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10670629).

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.604G>A	p.Ala202Thr	missense	Exon 6 of 7	NP_113608.1	Q9BYD2
	MRPL9	NM_001300733.2		c.502G>A	p.Ala168Thr	missense	Exon 5 of 6	NP_001287662.1	Q5SZR1
	MRPL9	NR_125331.2		n.661G>A		non_coding_transcript_exon	Exon 6 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL9	ENST00000368830.8	TSL:1 MANE Select	c.604G>A	p.Ala202Thr	missense	Exon 6 of 7	ENSP00000357823.3	Q9BYD2
	MRPL9	ENST00000368829.3	TSL:2	c.502G>A	p.Ala168Thr	missense	Exon 5 of 6	ENSP00000357822.3	Q5SZR1
	MRPL9	ENST00000467306.5	TSL:2	n.*275G>A		non_coding_transcript_exon	Exon 6 of 7	ENSP00000492374.1	A0A1W2PRK9

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1320620 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 660866

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29040

American (AMR) AF: 0.00 AC: 0 AN: 34886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23864

East Asian (EAS) AF: 0.00 AC: 0 AN: 37708

South Asian (SAS) AF: 0.00 AC: 0 AN: 76548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4828

European-Non Finnish (NFE) AF: 9.88e-7 AC: 1 AN: 1011982

Other (OTH) AF: 0.00 AC: 0 AN: 54922

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 24

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	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.8
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.018
Sift	Uncertain	0.020	D
Sift4G	Benign	0.18	T
Polyphen		0.048	B
Vest4		0.054
MutPred		0.28		Gain of methylation at K207 (P = 0.1147)
MVP		0.34
MPC		0.53
ClinPred		0.38	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.37
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chr1-151733360;