Genetic Variant RPL13A:c.403-5C>T (chr19-49491420-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012423.4(RPL13A):c.403-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,072,062 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00019 ( 1 hom., cov: 15)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

RPL13A
NM_012423.4 splice_region, intron

Scores

Splicing: ADA: 0.00008781

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0200

Variant links:

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]

RPL13A links:

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]

SNORD35A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BS2

High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RPL13A	NM_012423.4 link	c.403-5C>T	splice_region_variant, intron_variant	Intron 6 of 7	ENST00000391857.9	NP_036555.1	P40429A0A384ME37
RPL13A	NM_001270491.2 link	c.220-5C>T	splice_region_variant, intron_variant	Intron 5 of 6		NP_001257420.1	P40429Q8J015
RPL13A	NR_073024.2 link	n.415-5C>T	splice_region_variant, intron_variant	Intron 6 of 7
SNORD35A	NR_000018.1 link	n.*160C>T	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL13A	ENST00000391857.9 link	c.403-5C>T		splice_region_variant, intron_variant	Intron 6 of 7	1	NM_012423.4	ENSP00000375730.4		P40429

Frequencies

GnomAD3 genomes

AF:

0.000193

AC:

AN:

67430

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000978

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000106

Gnomad OTH

AF:

0.00247

GnomAD3 exomes

AF:

0.000108

AC:

AN:

120748

Hom.:

AF XY:

0.000121

AC XY:

AN XY:

65884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000209

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000136

AC:

137

AN:

1004590

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

502782

show subpopulations

Gnomad4 AFR exome

AF:

0.0000460

Gnomad4 AMR exome

AF:

0.000274

Gnomad4 ASJ exome

AF:

0.0000504

Gnomad4 EAS exome

AF:

0.000359

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000397

Gnomad4 NFE exome

AF:

0.000142

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000193

AC:

AN:

67472

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

AN XY:

34200

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000977

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000106

Gnomad4 OTH

AF:

0.00244

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.3

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000088

dbscSNV1_RF

Benign

0.0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over