Genetic Variant RPL22L1:p.Arg107His (chr3-170866429-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001099645.2(RPL22L1):c.320G>A(p.Arg107His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,603,258 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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>A	p.Arg107His	missense	Exon 4 of 4	NP_001093115.1	Q6P5R6
RPL22L1	NM_001320451.2		c.317G>A	p.Arg106His	missense	Exon 4 of 4	NP_001307380.1	C9JYQ9
RPL22L1	NR_135259.2		n.415G>A		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>A	p.Arg107His	missense	Exon 4 of 4	ENSP00000346080.7	Q6P5R6
RPL22L1	ENST00000475836.5	TSL:1	n.*192G>A		non_coding_transcript_exon	Exon 4 of 4	ENSP00000418909.1	Q5JWX6
RPL22L1	ENST00000475836.5	TSL:1	n.*192G>A		3_prime_UTR	Exon 4 of 4	ENSP00000418909.1	Q5JWX6

Frequencies

GnomAD3 genomes

AF:

0.0000131

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000431

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1451070

Hom.:

Cov.:

AF XY:

0.0000153

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:

0.00

AC:

AN:

39432

South Asian (SAS)

AF:

0.0000833

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:

0.00000633

AC:

AN:

1106352

Other (OTH)

AF:

0.0000334

AC:

AN:

59942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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:

0.0000131

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.068

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

0.10

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.0

PhyloP100

7.9

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.31

Sift

Benign

0.082

Sift4G

Benign

0.083

Polyphen

0.23

Vest4

0.73

MutPred

0.69

Loss of disorder (P = 0.0936)

MVP

0.45

MPC

0.027

ClinPred

0.97

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.58

Mutation Taster

=55/45

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over