chr19-49491452-G-C

Variant names:

• chr19-49491452-G-C
• rs1430214653
• NM_012423.4:c.430G>C

Variant summary

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

The NM_012423.4(RPL13A):​c.430G>C​(p.Glu144Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000872 in 1,146,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: RPL13A NM_012423.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.63
• Publications: 0 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]

SNORD35A (HGNC:10162): (small nucleolar RNA, C/D box 35A) Predicted to act upstream of or within glucose metabolic process; insulin secretion; and reactive oxygen species metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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_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.430G>C	p.Glu144Gln	missense	Exon 7 of 8	NP_036555.1	P40429
	RPL13A	NM_001270491.2		c.247G>C	p.Glu83Gln	missense	Exon 6 of 7	NP_001257420.1	Q8J015
	RPL13A	NR_073024.2		n.442G>C		non_coding_transcript_exon	Exon 7 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL13A	ENST00000391857.9	TSL:1 MANE Select	c.430G>C	p.Glu144Gln	missense	Exon 7 of 8	ENSP00000375730.4	P40429
	RPL13A	ENST00000624069.3	TSL:1	n.*273G>C		non_coding_transcript_exon	Exon 7 of 8	ENSP00000485546.1	A0A096LPE0
	RPL13A	ENST00000624069.3	TSL:1	n.*273G>C		3_prime_UTR	Exon 7 of 8	ENSP00000485546.1	A0A096LPE0

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 8.72e-7 AC: 1 AN: 1146834 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 567212

African (AFR) AF: 0.00 AC: 0 AN: 26702

American (AMR) AF: 0.00 AC: 0 AN: 34256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21904

East Asian (EAS) AF: 0.00 AC: 0 AN: 30066

South Asian (SAS) AF: 0.00 AC: 0 AN: 76134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4582

European-Non Finnish (NFE) AF: 0.00000114 AC: 1 AN: 875970

Other (OTH) AF: 0.00 AC: 0 AN: 47574

GnomAD4 genome Cov.: 29

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	0.96
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		9.6
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.23
Sift	Benign	0.046	D
Sift4G	Benign	0.11	T
Polyphen		0.97	D
Vest4		0.77
MutPred		0.40		Gain of MoRF binding (P = 0.062)
MVP		0.71
MPC		1.0
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.36
gMVP		0.80
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1430214653; hg19: chr19-49994709;