chr22-39316779-T-G

Variant names:

• chr22-39316779-T-G
• NM_000967.4:c.428A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000967.4(RPL3):​c.428A>C​(p.Lys143Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPL3 NM_000967.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.15
• Publications: 0 publications found

Genes affected

RPL3 (HGNC:10332): (ribosomal protein L3) Ribosomes, the complexes 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 L3P family of ribosomal proteins and it is located in the cytoplasm. The protein can bind to the HIV-1 TAR mRNA, and it has been suggested that the protein contributes to tat-mediated transactivation. This gene is co-transcribed with several small nucleolar RNA genes, which are located in several of this gene's introns. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. 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]

SNORD139 (HGNC:50421): (small nucleolar RNA, C/D box 139) Intronic regions of ribosomal protein genes can harbor noncoding small nucleolar RNAs (snoRNAs), like U86, which are generated during pre-mRNA processing. snoRNAs form part of the small nucleolar ribonucleoprotein particles (snoRNPs) involved in pre-rRNA processing and modification. snoRNAs of the box C/D class, like U86, function in 2-prime-O-ribose methylation of rRNAs (Duga et al., 2000 [PubMed 10684968]).[supplied by OMIM, Mar 2008]

ACMG classification

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=0.34667778).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000967.4. 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
	RPL3	NM_000967.4	MANE Select	c.428A>C	p.Lys143Thr	missense	Exon 4 of 10	NP_000958.1	P39023
	RPL3	NM_001033853.2		c.384+44A>C		intron	N/A	NP_001029025.1
	SNORD139	NR_000026.1		n.*63A>C		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL3	ENST00000216146.9	TSL:1 MANE Select	c.428A>C	p.Lys143Thr	missense	Exon 4 of 10	ENSP00000346001.3	P39023
	RPL3	ENST00000401609.5	TSL:1	c.272A>C	p.Lys91Thr	missense	Exon 3 of 9	ENSP00000386101.1	G5E9G0
	RPL3	ENST00000465618.5	TSL:1	n.1268A>C		non_coding_transcript_exon	Exon 4 of 10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.1
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.22
Sift	Uncertain	0.024	D
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.52		Loss of ubiquitination at K143 (P = 0.0183)
MVP		0.43
MPC		1.3
ClinPred		0.97	D
GERP RS		4.0
Varity_R		0.33
gMVP		0.71
Mutation Taster		=48/52	disease causing

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

hg19: chr22-39712784;