Genetic Variant RPL12:p.Val12Ile (chr9-127451284-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000976.4(RPL12):c.34G>A(p.Val12Ile) 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. 12/21 in silico tools predict 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. V12L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RPL12
NM_000976.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.74

Publications

0 publications found

Variant links:

Genes affected

RPL12 (HGNC:10302): (ribosomal protein L12) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L11P family of ribosomal proteins. It is located in the cytoplasm. The protein binds directly to the 26S rRNA. This gene is co-transcribed with the U65 snoRNA, which is located in its fourth intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPL12 links:

LRSAM1 (HGNC:25135): (leucine rich repeat and sterile alpha motif containing 1) This gene encodes a ring finger protein involved in a variety of functions, including regulation of signaling pathways and cell adhesion, mediation of self-ubiquitylation, and involvement in cargo sorting during receptor endocytosis. Mutations in this gene have been associated with Charcot-Marie-Tooth disease. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jan 2012]

LRSAM1 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease axonal type 2P
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

LRSAM1 links:

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ACMG classification

Classification was made for transcript

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=0.19447532).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000976.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL12	NM_000976.4	MANE Select	c.34G>A	p.Val12Ile	missense	Exon 1 of 7	NP_000967.1	P30050-1
LRSAM1	NM_001005373.4	MANE Select	c.-574C>T		upstream_gene	N/A	NP_001005373.1	Q6UWE0-1
LRSAM1	NM_001384142.1		c.-1591C>T		upstream_gene	N/A	NP_001371071.1	Q6UWE0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL12	ENST00000361436.10	TSL:1 MANE Select	c.34G>A	p.Val12Ile	missense	Exon 1 of 7	ENSP00000354739.5	P30050-1
RPL12	ENST00000536368.1	TSL:1	c.34G>A	p.Val12Ile	missense	Exon 1 of 6	ENSP00000441179.1	P30050-2
RPL12	ENST00000886311.1		c.34G>A	p.Val12Ile	missense	Exon 1 of 7	ENSP00000556370.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

Eigen

Benign

-0.23

Eigen_PC

Benign

0.024

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.0051

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

PhyloP100

3.7

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.27

REVEL

Benign

0.071

Sift

Benign

0.54

Sift4G

Benign

0.52

Polyphen

0.0010

Vest4

0.28

MutPred

0.35

Gain of sheet (P = 0.0101)

MVP

0.47

MPC

0.55

ClinPred

0.66

GERP RS

5.6

PromoterAI

0.13

Neutral

(source)

Varity_R

0.23

gMVP

0.22

Mutation Taster

=81/19

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over