Variant 19-49491420-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_012423.4(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
NM_012423.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0004453

Clinical Significance

Benign criteria provided, single submitter B:1

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 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_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
RPL13A	NM_012423.4 linkuse as main transcript	c.403-5C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000391857.9
RPL13A	NM_001270491.2 linkuse as main transcript	c.220-5C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
RPL13A	NR_073024.2 linkuse as main transcript	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	Appris	UniProt
RPL13A	ENST00000391857.9 linkuse as main transcript	c.403-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_012423.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

5853

AN:

67268

Hom.:

684

Cov.:

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

show subpopulations

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.:

AF XY:

0.0582

AC XY:

29222

AN XY:

501894

show subpopulations

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.:

AF XY:

0.0793

AC XY:

2706

AN XY:

34122

show subpopulations

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.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over