ENST00000524864.1:n.129_130insC

Variant names:

• chr11-119018537-A-AG
• rs11440855
• ENST00000937795.1:c.-254_-253insC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000524864.1(RPS25):​n.129_130insC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (76189 hom., cov: 0)
  • Exomes 𝑓: 1.0 (245915 hom.)
• Consequence: RPS25 ENST00000524864.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.04
• Publications: 4 publications found

Genes affected

RPS25 (HGNC:10413): (ribosomal protein S25) 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 S25E family of ribosomal proteins. It is located in the cytoplasm. 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]

ENSG00000300421 (HGNC:):

TRAPPC4 (HGNC:19943): (trafficking protein particle complex subunit 4) Involved in autophagy and endoplasmic reticulum to Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

TRAPPC4 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP6: Variant 11-119018537-A-AG is Benign according to our data. Variant chr11-119018537-A-AG is described in ClinVar as Benign. ClinVar VariationId is 1236244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000524864.1. 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
	TRAPPC4	NM_016146.6	MANE Select	c.-259_-258insG		upstream_gene	N/A	NP_057230.1	Q9Y296-1
	RPS25	NM_001028.3	MANE Select	c.-254_-253insC		upstream_gene	N/A	NP_001019.1	P62851
	TRAPPC4	NM_001318488.2		c.-259_-258insG		upstream_gene	N/A	NP_001305417.1	J3KP27

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS25	ENST00000937795.1		c.-254_-253insC		5_prime_UTR	Exon 1 of 5	ENSP00000607854.1
	RPS25	ENST00000942362.1		c.-254_-253insC		5_prime_UTR	Exon 1 of 5	ENSP00000612421.1
	RPS25	ENST00000937796.1		c.-254_-253insC		5_prime_UTR	Exon 1 of 5	ENSP00000607855.1

Frequencies

GnomAD3 genomes AF: 1.00 AC: 152270 AN: 152280 Hom.: 76130 Cov.: 0

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 0.999

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD4 exome AF: 1.00 AC: 491867 AN: 491904 Hom.: 245915 Cov.: 5 AF XY: 1.00 AC XY: 259579 AN XY: 259594

African (AFR) AF: 1.00 AC: 13134 AN: 13134

American (AMR) AF: 1.00 AC: 19832 AN: 19832

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 14118 AN: 14118

East Asian (EAS) AF: 1.00 AC: 31571 AN: 31572

South Asian (SAS) AF: 1.00 AC: 47992 AN: 47994

European-Finnish (FIN) AF: 1.00 AC: 30549 AN: 30564

Middle Eastern (MID) AF: 1.00 AC: 2126 AN: 2126

European-Non Finnish (NFE) AF: 1.00 AC: 304923 AN: 304942

Other (OTH) AF: 1.00 AC: 27622 AN: 27622

GnomAD4 genome AF: 1.00 AC: 152388 AN: 152398 Hom.: 76189 Cov.: 0 AF XY: 1.00 AC XY: 74518 AN XY: 74524

African (AFR) AF: 1.00 AC: 41598 AN: 41598

American (AMR) AF: 1.00 AC: 15312 AN: 15312

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 1.00 AC: 4834 AN: 4834

European-Finnish (FIN) AF: 0.999 AC: 10622 AN: 10628

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68042 AN: 68046

Other (OTH) AF: 1.00 AC: 2116 AN: 2116

Alfa AF: 1.00 Hom.: 8166

Bravo AF: 1.00

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

ClinVar submissions

Significance: 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
PhyloP100		-1.0
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs11440855; hg19: chr11-118889247; COSMIC: COSV57722063; COSMIC: COSV57722063;