Genetic Variant RPL22L1:p.Arg107Pro (chr3-170866429-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001099645.2(RPL22L1):c.320G>C(p.Arg107Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,603,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R107L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

RPL22L1
NM_001099645.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.88

Publications

0 publications found

Variant links:

Genes affected

RPL22L1 (HGNC:27610): (ribosomal protein L22 like 1) Predicted to enable RNA binding activity. Predicted to be a structural constituent of ribosome. Predicted to be involved in cytoplasmic translation. Predicted to be located in ribosome. [provided by Alliance of Genome Resources, Apr 2022]

RPL22L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.763

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099645.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL22L1	NM_001099645.2	MANE Select	c.320G>C	p.Arg107Pro	missense	Exon 4 of 4	NP_001093115.1	Q6P5R6
RPL22L1	NM_001320451.2		c.317G>C	p.Arg106Pro	missense	Exon 4 of 4	NP_001307380.1	C9JYQ9
RPL22L1	NR_135259.2		n.415G>C		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL22L1	ENST00000295830.13	TSL:1 MANE Select	c.320G>C	p.Arg107Pro	missense	Exon 4 of 4	ENSP00000346080.7	Q6P5R6
RPL22L1	ENST00000475836.5	TSL:1	n.*192G>C		non_coding_transcript_exon	Exon 4 of 4	ENSP00000418909.1	Q5JWX6
RPL22L1	ENST00000475836.5	TSL:1	n.*192G>C		3_prime_UTR	Exon 4 of 4	ENSP00000418909.1	Q5JWX6

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000172

AC:

AN:

231902

AF XY:

0.00000799

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000117

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000965

AC:

AN:

1451072

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

720694

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33322

American (AMR)

AF:

0.00

AC:

AN:

43508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25902

East Asian (EAS)

AF:

0.0000507

AC:

AN:

39432

South Asian (SAS)

AF:

0.000131

AC:

AN:

84078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52782

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106354

Other (OTH)

AF:

0.00

AC:

AN:

59942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000331

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.60

MutationAssessor

Pathogenic

3.5

PhyloP100

7.9

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-6.5

REVEL

Uncertain

0.54

Sift

Uncertain

0.020

Sift4G

Uncertain

0.020

Polyphen

0.65

Vest4

0.92

MutPred

0.71

Gain of phosphorylation at Y108 (P = 0.083)

MVP

0.62

MPC

0.031

ClinPred

0.69

GERP RS

3.6

Varity_R

0.97

gMVP

0.85

Mutation Taster

=37/63

disease causing

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over