Genetic Variant NM_000983.4:c.5C>G (chr1-6199569-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000983.4(RPL22):c.5C>G(p.Ala2Gly) 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. 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. A2V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

RPL22
NM_000983.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.66

Publications

3 publications found

Variant links:

Genes affected

RPL22 (HGNC:10315): (ribosomal protein L22) 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 cytoplasmic ribosomal protein that is a component of the 60S subunit. The protein belongs to the L22E family of ribosomal proteins. Its initiating methionine residue is post-translationally removed. The protein can bind specifically to Epstein-Barr virus-encoded RNAs (EBERs) 1 and 2. The mouse protein has been shown to be capable of binding to heparin. Transcript variants utilizing alternative polyA signals exist. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. It was previously thought that this gene mapped to 3q26 and that it was fused to the acute myeloid leukemia 1 (AML1) gene located at 21q22 in some therapy-related myelodysplastic syndrome patients with 3;21 translocations; however, these fusions actually involve a ribosomal protein L22 pseudogene located at 3q26, and this gene actually maps to 1p36.3-p36.2. [provided by RefSeq, Jul 2008]

RPL22 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2975104).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000983.4. 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
	RPL22	NM_000983.4	MANE Select	c.5C>G	p.Ala2Gly	missense	Exon 1 of 4	NP_000974.1	P35268

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL22	ENST00000234875.9	TSL:1 MANE Select	c.5C>G	p.Ala2Gly	missense	Exon 1 of 4	ENSP00000346088.3	P35268
RPL22	ENST00000929467.1		c.5C>G	p.Ala2Gly	missense	Exon 1 of 5	ENSP00000599526.1
RPL22	ENST00000929466.1		c.5C>G	p.Ala2Gly	missense	Exon 1 of 4	ENSP00000599525.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

177676

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.75

M_CAP

Benign

0.066

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.1

PhyloP100

5.7

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.1

REVEL

Benign

0.22

Sift

Benign

0.046

Sift4G

Uncertain

0.027

Polyphen

0.0

Vest4

0.43

MutPred

0.34

Gain of sheet (P = 0.0221)

MVP

0.57

MPC

2.6

ClinPred

0.91

GERP RS

2.7

PromoterAI

-0.25

Neutral

(source)

Varity_R

0.15

gMVP

0.45

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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