chr19-49491420-C-G

Position:

• chr19-49491420-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The ENST00000391857.9(RPL13A):​c.403-5C>G 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 0.087 (687 hom., cov: 15)
  • Exomes 𝑓: 0.057 (3793 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPL13A ENST00000391857.9 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0004453
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0200

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-49491420-C-G is Benign according to our data. Variant chr19-49491420-C-G is described in ClinVar as [Benign]. Clinvar id is 770467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL13A	NM_012423.4	c.403-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000391857.9	NP_036555.1
RPL13A	NM_001270491.2	c.220-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001257420.1
RPL13A	NR_073024.2	n.415-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL13A	ENST00000391857.9	c.403-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_012423.4	ENSP00000375730	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5853 AN: 67268 Hom.: 684 Cov.: 15 FAILED QC

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.0300

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.0280

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.0412

Gnomad NFE AF: 0.0457

Gnomad OTH AF: 0.0953

GnomAD3 exomes AF: 0.0764 AC: 9226 AN: 120748 Hom.: 323 AF XY: 0.0745 AC XY: 4907 AN XY: 65884

Gnomad AFR exome AF: 0.333

Gnomad AMR exome AF: 0.0613

Gnomad ASJ exome AF: 0.0597

Gnomad EAS exome AF: 0.0511

Gnomad SAS exome AF: 0.0751

Gnomad FIN exome AF: 0.0599

Gnomad NFE exome AF: 0.0654

Gnomad OTH exome AF: 0.0753

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0574 AC: 57527 AN: 1002848 Hom.: 3793 Cov.: 22 AF XY: 0.0582 AC XY: 29222 AN XY: 501894

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.0682

Gnomad4 ASJ exome AF: 0.0530

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.0697

Gnomad4 FIN exome AF: 0.0633

Gnomad4 NFE exome AF: 0.0458

Gnomad4 OTH exome AF: 0.0758

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0870 AC: 5858 AN: 67310 Hom.: 687 Cov.: 15 AF XY: 0.0793 AC XY: 2706 AN XY: 34122

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.0399

Gnomad4 ASJ AF: 0.0429

Gnomad4 EAS AF: 0.0277

Gnomad4 SAS AF: 0.0494

Gnomad4 FIN AF: 0.0112

Gnomad4 NFE AF: 0.0456

Gnomad4 OTH AF: 0.0944

Alfa AF: 0.0379 Hom.: 17

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00045
dbscSNV1_RF	Benign	0.030
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: rs115089990; hg19: chr19-49994677;