rs1383902242

Variant names:

• chr3-170868363-T-A
• rs1383902242
• NM_001099645.2:c.37A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-170868363-T-A
• chr3-170868363-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001099645.2(RPL22L1):​c.37A>T​(p.Thr13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. T13A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RPL22L1 NM_001099645.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06421167).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL22L1	NM_001099645.2	MANE Select	c.37A>T	p.Thr13Ser	missense	Exon 2 of 4	NP_001093115.1	Q6P5R6
	RPL22L1	NM_001320451.2		c.34A>T	p.Thr12Ser	missense	Exon 2 of 4	NP_001307380.1	C9JYQ9
	RPL22L1	NR_135259.2		n.65A>T		non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL22L1	ENST00000295830.13	TSL:1 MANE Select	c.37A>T	p.Thr13Ser	missense	Exon 2 of 4	ENSP00000346080.7	Q6P5R6
	RPL22L1	ENST00000475836.5	TSL:1	n.37A>T		non_coding_transcript_exon	Exon 2 of 4	ENSP00000418909.1	Q5JWX6
	RPL22L1	ENST00000466674.5	TSL:3	c.97A>T	p.Thr33Ser	missense	Exon 2 of 4	ENSP00000419713.1	H0Y8C2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456736 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 724744

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33346

American (AMR) AF: 0.00 AC: 0 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4590

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109358

Other (OTH) AF: 0.00 AC: 0 AN: 60144

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.68	N
PhyloP100		0.43
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.016
Sift	Benign	0.35	T
Sift4G	Benign	0.38	T
Polyphen		0.037	B
Vest4		0.11
MutPred		0.34		Gain of disorder (P = 0.0339)
MVP		0.16
MPC		0.025
ClinPred		0.13	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.092
gMVP		0.12
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs1383902242; hg19: chr3-170586152;