rs7113753

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-119018668-G-A
• chr11-119018668-G-C
• chr11-119018668-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000937795.1(RPS25):​c.-384C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,088,050 control chromosomes in the GnomAD database, including 53,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (14113 hom., cov: 33)
  • Exomes 𝑓: 0.27 (39554 hom.)
• Consequence: RPS25 ENST00000937795.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.22
• Publications: 14 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-119018668-G-A is Benign according to our data. Variant chr11-119018668-G-A is described in ClinVar as Benign. ClinVar VariationId is 1240845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

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>A		upstream_gene	N/A	NP_057230.1	Q9Y296-1
	TRAPPC4	NM_001318488.2		c.-128G>A		upstream_gene	N/A	NP_001305417.1	J3KP27
	TRAPPC4	NM_001318490.2		c.-128G>A		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>T		5_prime_UTR	Exon 1 of 5	ENSP00000607854.1
	RPS25	ENST00000942362.1		c.-384C>T		5_prime_UTR	Exon 1 of 5	ENSP00000612421.1
	RPS25	ENST00000937796.1		c.-384C>T		5_prime_UTR	Exon 1 of 5	ENSP00000607855.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58414 AN: 151732 Hom.: 14064 Cov.: 33

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.272 AC: 254646 AN: 936200 Hom.: 39554 Cov.: 13 AF XY: 0.275 AC XY: 130833 AN XY: 476148

African (AFR) AF: 0.703 AC: 15959 AN: 22686

American (AMR) AF: 0.209 AC: 7696 AN: 36748

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 3908 AN: 18726

East Asian (EAS) AF: 0.155 AC: 5748 AN: 37054

South Asian (SAS) AF: 0.357 AC: 23734 AN: 66536

European-Finnish (FIN) AF: 0.307 AC: 12945 AN: 42214

Middle Eastern (MID) AF: 0.252 AC: 861 AN: 3420

European-Non Finnish (NFE) AF: 0.257 AC: 171396 AN: 666594

Other (OTH) AF: 0.294 AC: 12399 AN: 42222

GnomAD4 genome AF: 0.385 AC: 58517 AN: 151850 Hom.: 14113 Cov.: 33 AF XY: 0.384 AC XY: 28479 AN XY: 74252

African (AFR) AF: 0.693 AC: 28660 AN: 41354

American (AMR) AF: 0.279 AC: 4270 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3464

East Asian (EAS) AF: 0.149 AC: 771 AN: 5172

South Asian (SAS) AF: 0.373 AC: 1802 AN: 4832

European-Finnish (FIN) AF: 0.324 AC: 3425 AN: 10566

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.264 AC: 17911 AN: 67874

Other (OTH) AF: 0.343 AC: 721 AN: 2104

Alfa AF: 0.305 Hom.: 1693

Bravo AF: 0.394

Asia WGS AF: 0.298 AC: 1039 AN: 3478

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	-0.90
CADD	Benign	0.75
DANN	Benign	0.82
PhyloP100		-1.2
PromoterAI		0.0020	Neutral
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: rs7113753; hg19: chr11-118889378; COSMIC: COSV57722521; COSMIC: COSV57722521;