19-49491421-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012423.4(RPL13A):c.403-4G>A variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002410
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
RPL13A	NM_012423.4	c.403-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000391857.9
RPL13A	NM_001270491.2	c.220-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
RPL13A	NR_073024.2	n.415-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL13A	ENST00000391857.9	c.403-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_012423.4	P1

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 517 AN: 15690 Hom.: 20 Cov.: 0

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0152

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: 0.000380

Gnomad OTH AF: 0.0135

GnomAD3 exomes AF: 0.0188 AC: 391 AN: 20758 Hom.: 13 AF XY: 0.0155 AC XY: 172 AN XY: 11118

Gnomad AFR exome AF: 0.173

Gnomad AMR exome AF: 0.0126

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000336

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.0141

GnomAD4 exome AF: 0.00859 AC: 1439 AN: 167502 Hom.: 53 Cov.: 5 AF XY: 0.00759 AC XY: 640 AN XY: 84290

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.000244

Gnomad4 EAS exome AF: 0.000250

Gnomad4 SAS exome AF: 0.000675

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000309

Gnomad4 OTH exome AF: 0.0169

GnomAD4 genome AF: 0.0331 AC: 520 AN: 15712 Hom.: 20 Cov.: 0 AF XY: 0.0409 AC XY: 280 AN XY: 6846

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0151

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000379

Gnomad4 OTH AF: 0.0135

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.43
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
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

Other links and lift over

dbSNP: rs115924751; hg19: chr19-49994678;