Genetic Variant NM_031420.4:c.601G>A (chr1-151760887-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_031420.4(MRPL9):c.601G>A(p.Val201Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000733 in 1,364,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

MRPL9
NM_031420.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.56

Variant links:

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]

MRPL9 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2835308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL9	NM_031420.4 link	c.601G>A	p.Val201Ile	missense_variant	Exon 6 of 7	ENST00000368830.8	NP_113608.1	Q9BYD2
MRPL9	NM_001300733.2 link	c.499G>A	p.Val167Ile	missense_variant	Exon 5 of 6		NP_001287662.1	Q9BYD2Q5SZR1
MRPL9	NR_125331.2 link	n.658G>A		non_coding_transcript_exon_variant	Exon 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL9	ENST00000368830.8 link	c.601G>A	p.Val201Ile	missense_variant	Exon 6 of 7	1	NM_031420.4	ENSP00000357823.3		Q9BYD2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.33e-7

AC:

AN:

1364428

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

680446

show subpopulations

Gnomad4 AFR exome

AF:

0.0000345

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.601G>A (p.V201I) alteration is located in exon 6 (coding exon 6) of the MRPL9 gene. This alteration results from a G to A substitution at nucleotide position 601, causing the valine (V) at amino acid position 201 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

T;.

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.0060

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.69

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.023

D;D

Sift4G

Benign

0.087

T;T

Polyphen

1.0

D;.

Vest4

0.37

MutPred

0.49

Gain of catalytic residue at P203 (P = 0.0329);.;

MVP

0.39

MPC

0.97

ClinPred

0.90

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.086

gMVP

0.42

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