rs10181042

chr2-60997124-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144709.4(PUS10):c.468+9433G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,978 control chromosomes in the GnomAD database, including 12,818 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 0.40 (12818 hom., cov: 31)
• Consequence: PUS10 NM_144709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793

Genes affected

PUS10 (HGNC:26505): (pseudouridine synthase 10) Pseudouridination, the isomerization of uridine to pseudouridine, is the most common posttranscriptional nucleotide modification found in RNA and is essential for biologic functions such as spliceosome biogenesis. Pseudouridylate synthases, such as PUS10, catalyze pseudouridination of structural RNAs, including transfer, ribosomal, and splicing RNAs. These enzymes also act as RNA chaperones, facilitating the correct folding and assembly of tRNAs (McCleverty et al., 2007 [PubMed 17900615]).[supplied by OMIM, May 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUS10	NM_144709.4	c.468+9433G>A		intron_variant		ENST00000316752.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUS10	ENST00000316752.11	c.468+9433G>A		intron_variant		1	NM_144709.4	P1
PUS10	ENST00000602599.1	n.735+9433G>A		intron_variant, non_coding_transcript_variant		1
PUS10	ENST00000407787.5	c.468+9433G>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60676 AN: 151860 Hom.: 12800 Cov.: 31

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.0391

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.400 AC: 60738 AN: 151978 Hom.: 12818 Cov.: 31 AF XY: 0.392 AC XY: 29128 AN XY: 74268

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.0390

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.425

Alfa AF: 0.402 Hom.: 27738

Bravo AF: 0.395

Asia WGS AF: 0.139 AC: 482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.26
Dann	Benign	0.29

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: rs10181042; hg19: chr2-61224259;