rs11131194

Variant names:

• chr3-9838742-C-T
• rs11131194
• NM_173659.5:c.840+290G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173659.5(RPUSD3):​c.840+290G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,016 control chromosomes in the GnomAD database, including 19,980 homozygotes. 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: 𝑓 0.48 (19980 hom., cov: 32)
• Consequence: RPUSD3 NM_173659.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725
• Publications: 12 publications found

Genes affected

RPUSD3 (HGNC:28437): (RNA pseudouridine synthase D3) This gene encodes a protein that functions in the assembly of the mitochondrial ribosome by adding a pseudouridine group to 16S rRNA. Loss of this gene results in causes defects in mitochondrial protein production. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2017]

TTLL3 (HGNC:24483): (tubulin tyrosine ligase like 3) Enables protein-glycine ligase activity. Predicted to be involved in axoneme assembly and flagellated sperm motility. Predicted to be located in axoneme; microtubule cytoskeleton; and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPUSD3	NM_173659.5	c.840+290G>A		intron_variant	Intron 8 of 8	ENST00000383820.10	NP_775930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPUSD3	ENST00000383820.10	c.840+290G>A		intron_variant	Intron 8 of 8	1	NM_173659.5	ENSP00000373331.6

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73687 AN: 151898 Hom.: 19983 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.511

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.485 AC: 73700 AN: 152016 Hom.: 19980 Cov.: 32 AF XY: 0.483 AC XY: 35877 AN XY: 74278

African (AFR) AF: 0.255 AC: 10580 AN: 41468

American (AMR) AF: 0.469 AC: 7160 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2381 AN: 3468

East Asian (EAS) AF: 0.237 AC: 1227 AN: 5170

South Asian (SAS) AF: 0.563 AC: 2708 AN: 4814

European-Finnish (FIN) AF: 0.579 AC: 6098 AN: 10532

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41491 AN: 67962

Other (OTH) AF: 0.513 AC: 1084 AN: 2114

Alfa AF: 0.569 Hom.: 112378

Bravo AF: 0.465

Asia WGS AF: 0.395 AC: 1372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.35
PhyloP100		-0.72
Mutation Taster		=100/0	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: rs11131194; hg19: chr3-9880426;