chr19-49487634-C-G

Variant names:

• chr19-49487634-C-G
• rs570610827
• NM_012423.4:c.5C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM1 BP4 BS2

The NM_012423.4(RPL13A):​c.5C>G​(p.Ala2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000423 in 1,419,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: RPL13A NM_012423.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.85
• Publications: 1 publications found

Genes affected

RPL13A (HGNC:10304): (ribosomal protein L13a) 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 member of the L13P family of ribosomal proteins that is a component of the 60S subunit. The encoded protein also plays a role in the repression of inflammatory genes as a component of the IFN-gamma-activated inhibitor of translation (GAIT) complex. This gene is co-transcribed with the small nucleolar RNA genes U32, U33, U34, and U35, which are located in the second, fourth, fifth, and sixth introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ENSG00000273189 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM1: In a modified_residue N-acetylalanine (size 0) in uniprot entity RL13A_HUMAN
• BP4: Computational evidence support a benign effect (MetaRNN=0.37149262).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012423.4. 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
	RPL13A	NM_012423.4	MANE Select	c.5C>G	p.Ala2Gly	missense	Exon 1 of 8	NP_036555.1	P40429
	RPL13A	NM_001270491.2		c.-103C>G		5_prime_UTR	Exon 1 of 7	NP_001257420.1	Q8J015
	RPL13A	NR_073024.2		n.27C>G		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL13A	ENST00000391857.9	TSL:1 MANE Select	c.5C>G	p.Ala2Gly	missense	Exon 1 of 8	ENSP00000375730.4	P40429
	RPL13A	ENST00000624069.3	TSL:1	n.5C>G		non_coding_transcript_exon	Exon 1 of 8	ENSP00000485546.1	A0A096LPE0
	RPL13A	ENST00000961389.1		c.5C>G	p.Ala2Gly	missense	Exon 1 of 8	ENSP00000631448.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000552 AC: 1 AN: 181026 AF XY: 0.00

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: 0.0000131

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000423 AC: 6 AN: 1419726 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 702820

African (AFR) AF: 0.00 AC: 0 AN: 31924

American (AMR) AF: 0.00 AC: 0 AN: 37714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25140

East Asian (EAS) AF: 0.00 AC: 0 AN: 37324

South Asian (SAS) AF: 0.00 AC: 0 AN: 80838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.00000366 AC: 4 AN: 1091866

Other (OTH) AF: 0.0000341 AC: 2 AN: 58730

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000842 AC: 1

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	Benign	0.10
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	34
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.8
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.15
Sift	Benign	0.18	T
Sift4G	Benign	0.15	T
Polyphen		0.0010	B
Vest4		0.54
MutPred		0.27		Gain of disorder (P = 0.0624)
MVP		0.40
MPC		0.48
ClinPred		0.39	T
GERP RS		3.5
PromoterAI		-0.73	Under-expression
Varity_R		0.092
gMVP		0.45
Mutation Taster		=82/18	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: rs570610827; hg19: chr19-49990891;