11-119018537-A-AGTACTATAGCGCTG

Variant names:

• chr11-119018537-A-AGTACTATAGCGCTG
• rs11440855
• ENST00000937795.1:c.-254_-253insCAGCGCTATAGTAC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000937795.1(RPS25):​c.-254_-253insCAGCGCTATAGTAC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: RPS25 ENST00000937795.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000937795.1. 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_-258insGTACTATAGCGCTG		upstream_gene	N/A	NP_057230.1	Q9Y296-1
	RPS25	NM_001028.3	MANE Select	c.-254_-253insCAGCGCTATAGTAC		upstream_gene	N/A	NP_001019.1	P62851
	TRAPPC4	NM_001318488.2		c.-259_-258insGTACTATAGCGCTG		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_-253insCAGCGCTATAGTAC		5_prime_UTR	Exon 1 of 5	ENSP00000607854.1
	RPS25	ENST00000942362.1		c.-254_-253insCAGCGCTATAGTAC		5_prime_UTR	Exon 1 of 5	ENSP00000612421.1
	RPS25	ENST00000937796.1		c.-254_-253insCAGCGCTATAGTAC		5_prime_UTR	Exon 1 of 5	ENSP00000607855.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 5

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11440855; hg19: chr11-118889247;