ENST00000937795.1:c.-384C>G

Variant names:

• chr11-119018668-G-C
• rs7113753
• ENST00000937795.1:c.-384C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000937795.1(RPS25):​c.-384C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000299 in 937,656 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: RPS25 ENST00000937795.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 0 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]

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

ENSG00000300421 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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.-128G>C		upstream_gene	N/A	NP_057230.1	Q9Y296-1
	TRAPPC4	NM_001318488.2		c.-128G>C		upstream_gene	N/A	NP_001305417.1	J3KP27
	TRAPPC4	NM_001318490.2		c.-128G>C		upstream_gene	N/A	NP_001305419.1	E9PQE8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS25	ENST00000937795.1		c.-384C>G		5_prime_UTR	Exon 1 of 5	ENSP00000607854.1
	RPS25	ENST00000942362.1		c.-384C>G		5_prime_UTR	Exon 1 of 5	ENSP00000612421.1
	RPS25	ENST00000937796.1		c.-384C>G		5_prime_UTR	Exon 1 of 5	ENSP00000607855.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000299 AC: 28 AN: 937656 Hom.: 0 Cov.: 13 AF XY: 0.0000294 AC XY: 14 AN XY: 476832

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000880 AC: 2 AN: 22722

American (AMR) AF: 0.00 AC: 0 AN: 36782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18742

East Asian (EAS) AF: 0.00 AC: 0 AN: 37060

South Asian (SAS) AF: 0.0000300 AC: 2 AN: 66592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3428

European-Non Finnish (NFE) AF: 0.0000344 AC: 23 AN: 667830

Other (OTH) AF: 0.0000237 AC: 1 AN: 42254

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000433952), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.48
PhyloP100		-1.2
PromoterAI		0.016	Neutral

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: rs7113753; hg19: chr11-118889378;