rs74416259

Variant names:

• chr11-17077484-A-G
• rs74416259
• NM_001017.3:c.24-7T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-17077484-A-G
• chr11-17077484-A-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001017.3(RPS13):​c.24-7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,613,924 control chromosomes in the GnomAD database, including 13 homozygotes. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0023 (12 hom.)
• Consequence: RPS13 NM_001017.3 splice_region, intron
• Scores: Splicing: ADA: 0.0005039
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.40
• Publications: 2 publications found

Genes affected

RPS13 (HGNC:10386): (ribosomal protein S13) 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 ribosomal protein that is a component of the 40S subunit. The protein belongs to the S15P family of ribosomal proteins. It is located in the cytoplasm. The protein has been shown to bind to the 5.8S rRNA in rat. The gene product of the E. coli ortholog (ribosomal protein S15) functions at early steps in ribosome assembly. This gene is co-transcribed with two U14 small nucleolar RNA genes, which are located in its third and fifth introns. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

PIK3C2A (HGNC:8971): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha) The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is not sensitive to nanomolar levels of the inhibitor wortmanin. This protein was shown to be able to be activated by insulin and may be involved in integrin-dependent signaling. [provided by RefSeq, Jul 2008]

PIK3C2A Gene-Disease associations (from GenCC):

• oculocerebrodental syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 11-17077484-A-G is Benign according to our data. Variant chr11-17077484-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2641639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 327 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017.3. 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
	RPS13	NM_001017.3	MANE Select	c.24-7T>C		splice_region intron	N/A	NP_001008.1	P62277

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS13	ENST00000525634.6	TSL:1 MANE Select	c.24-7T>C		splice_region intron	N/A	ENSP00000435777.1	P62277
	RPS13	ENST00000924890.1		c.24-7T>C		splice_region intron	N/A	ENSP00000594949.1
	RPS13	ENST00000864174.1		c.24-7T>C		splice_region intron	N/A	ENSP00000534233.1

Frequencies

GnomAD3 genomes AF: 0.00215 AC: 327 AN: 152028 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00244

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00264 AC: 661 AN: 250822 AF XY: 0.00262

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.0272

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.00248

Gnomad OTH exome AF: 0.00344

GnomAD4 exome AF: 0.00228 AC: 3337 AN: 1461778 Hom.: 12 Cov.: 31 AF XY: 0.00230 AC XY: 1672 AN XY: 727196

African (AFR) AF: 0.000478 AC: 16 AN: 33480

American (AMR) AF: 0.00184 AC: 82 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 685 AN: 26122

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000893 AC: 77 AN: 86246

European-Finnish (FIN) AF: 0.000318 AC: 17 AN: 53418

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5764

European-Non Finnish (NFE) AF: 0.00200 AC: 2220 AN: 1111974

Other (OTH) AF: 0.00343 AC: 207 AN: 60390

GnomAD4 genome AF: 0.00215 AC: 327 AN: 152146 Hom.: 1 Cov.: 31 AF XY: 0.00195 AC XY: 145 AN XY: 74388

African (AFR) AF: 0.000337 AC: 14 AN: 41520

American (AMR) AF: 0.00216 AC: 33 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.000661 AC: 7 AN: 10590

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00244 AC: 166 AN: 67972

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00330 Hom.: 0

Bravo AF: 0.00216

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00376

EpiControl AF: 0.00368

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		2.4
PromoterAI		-0.045	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00050
dbscSNV1_RF	Benign	0.092
SpliceAI score (max)		0.010		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: rs74416259; hg19: chr11-17099031;