rs11131194

Positions:

• chr3-9838742-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RPUSD3	NM_173659.5	c.840+290G>A		intron_variant		ENST00000383820.10	NP_775930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPUSD3	ENST00000383820.10	c.840+290G>A		intron_variant		1	NM_173659.5	ENSP00000373331	P1

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

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.513

Alfa AF: 0.594 Hom.: 55604

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11131194; hg19: chr3-9880426;