19-49491421-G-A
Position:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_012423.4(RPL13A):c.403-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.033 ( 20 hom., cov: 0)
Exomes 𝑓: 0.0086 ( 53 hom. )
Consequence
RPL13A
NM_012423.4 splice_region, intron
NM_012423.4 splice_region, intron
Scores
2
Splicing: ADA: 0.00002410
2
Clinical Significance
Conservation
PhyloP100: -1.55
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 19-49491421-G-A is Benign according to our data. Variant chr19-49491421-G-A is described in ClinVar as [Benign]. Clinvar id is 775419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49491421-G-A is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0984 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RPL13A | NM_012423.4 | c.403-4G>A | splice_region_variant, intron_variant | ENST00000391857.9 | NP_036555.1 | |||
RPL13A | NM_001270491.2 | c.220-4G>A | splice_region_variant, intron_variant | NP_001257420.1 | ||||
RPL13A | NR_073024.2 | n.415-4G>A | splice_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RPL13A | ENST00000391857.9 | c.403-4G>A | splice_region_variant, intron_variant | 1 | NM_012423.4 | ENSP00000375730.4 |
Frequencies
GnomAD3 genomes AF: 0.0330 AC: 517AN: 15690Hom.: 20 Cov.: 0
GnomAD3 genomes
AF:
AC:
517
AN:
15690
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0188 AC: 391AN: 20758Hom.: 13 AF XY: 0.0155 AC XY: 172AN XY: 11118
GnomAD3 exomes
AF:
AC:
391
AN:
20758
Hom.:
AF XY:
AC XY:
172
AN XY:
11118
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00859 AC: 1439AN: 167502Hom.: 53 Cov.: 5 AF XY: 0.00759 AC XY: 640AN XY: 84290
GnomAD4 exome
AF:
AC:
1439
AN:
167502
Hom.:
Cov.:
5
AF XY:
AC XY:
640
AN XY:
84290
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0331 AC: 520AN: 15712Hom.: 20 Cov.: 0 AF XY: 0.0409 AC XY: 280AN XY: 6846
GnomAD4 genome
AF:
AC:
520
AN:
15712
Hom.:
Cov.:
0
AF XY:
AC XY:
280
AN XY:
6846
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 05, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at