19-49491420-C-G

Variant names:

• chr19-49491420-C-G
• rs115089990
• NM_012423.4:c.403-5C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_012423.4(RPL13A):​c.403-5C>G 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 0.087 (687 hom., cov: 15)
  • Exomes 𝑓: 0.057 (3793 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPL13A NM_012423.4 splice_region, intron
• Scores: Splicing: ADA: 0.0004453
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0200
• Publications: 3 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 770467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012423.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL13A	NM_012423.4	MANE Select	c.403-5C>G		splice_region intron	N/A	NP_036555.1	P40429
	RPL13A	NM_001270491.2		c.220-5C>G		splice_region intron	N/A	NP_001257420.1	Q8J015
	RPL13A	NR_073024.2		n.415-5C>G		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL13A	ENST00000391857.9	TSL:1 MANE Select	c.403-5C>G		splice_region intron	N/A	ENSP00000375730.4	P40429
	RPL13A	ENST00000624069.3	TSL:1	n.*246-5C>G		splice_region intron	N/A	ENSP00000485546.1	A0A096LPE0
	RPL13A	ENST00000467825.2	TSL:5	c.421-5C>G		splice_region intron	N/A	ENSP00000470037.2	M0QYS1

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 5853 AN: 67268 Hom.: 684 Cov.: 15

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

GnomAD2 exomes AF: 0.0764 AC: 9226 AN: 120748 AF XY: 0.0745

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 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

African (AFR) AF: 0.357 AC: 7699 AN: 21568

American (AMR) AF: 0.0682 AC: 1984 AN: 29084

Ashkenazi Jewish (ASJ) AF: 0.0530 AC: 1050 AN: 19812

East Asian (EAS) AF: 0.0625 AC: 1736 AN: 27760

South Asian (SAS) AF: 0.0697 AC: 4769 AN: 68470

European-Finnish (FIN) AF: 0.0633 AC: 1592 AN: 25164

Middle Eastern (MID) AF: 0.143 AC: 434 AN: 3030

European-Non Finnish (NFE) AF: 0.0458 AC: 35076 AN: 765940

Other (OTH) AF: 0.0758 AC: 3187 AN: 42020

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

African (AFR) AF: 0.242 AC: 3836 AN: 15856

American (AMR) AF: 0.0399 AC: 326 AN: 8178

Ashkenazi Jewish (ASJ) AF: 0.0429 AC: 68 AN: 1586

East Asian (EAS) AF: 0.0277 AC: 77 AN: 2776

South Asian (SAS) AF: 0.0494 AC: 77 AN: 1560

European-Finnish (FIN) AF: 0.0112 AC: 86 AN: 7660

Middle Eastern (MID) AF: 0.0444 AC: 8 AN: 180

European-Non Finnish (NFE) AF: 0.0456 AC: 1290 AN: 28264

Other (OTH) AF: 0.0944 AC: 77 AN: 816

Alfa AF: 0.0379 Hom.: 17

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.75
PhyloP100		0.020
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs115089990; hg19: chr19-49994677; COSMIC: COSV107214382; COSMIC: COSV107214382;