2-101004206-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000993.5(RPL31):c.156T>A(p.Phe52Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPL31 NM_000993.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75

Genes affected

RPL31 (HGNC:10334): (ribosomal protein L31) 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 ribosomal protein that is a component of the 60S subunit. The protein belongs to the L31E family of ribosomal proteins. It is located in the cytoplasm. Higher levels of expression of this gene in familial adenomatous polyps compared to matched normal tissues have been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.811

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL31	NM_000993.5	c.156T>A	p.Phe52Leu	missense_variant	3/5	ENST00000264258.8
RPL31	NM_001098577.3	c.156T>A	p.Phe52Leu	missense_variant	3/5
RPL31	NM_001099693.2	c.156T>A	p.Phe52Leu	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL31	ENST00000264258.8	c.156T>A	p.Phe52Leu	missense_variant	3/5	1	NM_000993.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.156T>A (p.F52L) alteration is located in exon 3 (coding exon 2) of the RPL31 gene. This alteration results from a T to A substitution at nucleotide position 156, causing the phenylalanine (F) at amino acid position 52 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;T;.;.;D;T;.;.;T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.81	D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Pathogenic	3.8	H;.;H;H;H;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-5.5	D;D;D;D;D;D;D;D;D
REVEL	Benign	0.25
Sift	Benign	0.052	T;T;D;T;T;T;D;T;T
Sift4G	Uncertain	0.046	D;T;T;D;D;T;D;D;T
Polyphen		0.27	B;B;.;.;B;B;D;.;B
Vest4		0.81
MutPred		0.77		Loss of methylation at K51 (P = 0.0317);Loss of methylation at K51 (P = 0.0317);Loss of methylation at K51 (P = 0.0317);Loss of methylation at K51 (P = 0.0317);Loss of methylation at K51 (P = 0.0317);Loss of methylation at K51 (P = 0.0317);Loss of methylation at K51 (P = 0.0317);Loss of methylation at K51 (P = 0.0317);Loss of methylation at K51 (P = 0.0317);
MVP		0.67
MPC		1.5
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.60
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-101620668;