rs10181042

Variant names:

• chr2-60997124-C-T
• rs10181042
• NM_144709.4:c.468+9433G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 56 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144709.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUS10	NM_144709.4	MANE Select	c.468+9433G>A		intron	N/A	NP_653310.2
	PUS10	NM_001322123.1		c.468+9433G>A		intron	N/A	NP_001309052.1
	PUS10	NM_001322124.1		c.468+9433G>A		intron	N/A	NP_001309053.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUS10	ENST00000316752.11	TSL:1 MANE Select	c.468+9433G>A		intron	N/A	ENSP00000326003.6
	PUS10	ENST00000602599.1	TSL:1	n.735+9433G>A		intron	N/A
	PUS10	ENST00000407787.6	TSL:2	c.468+9433G>A		intron	N/A	ENSP00000386074.1

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

African (AFR) AF: 0.473 AC: 19588 AN: 41418

American (AMR) AF: 0.312 AC: 4764 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1702 AN: 3468

East Asian (EAS) AF: 0.0390 AC: 202 AN: 5178

South Asian (SAS) AF: 0.186 AC: 897 AN: 4818

European-Finnish (FIN) AF: 0.409 AC: 4309 AN: 10544

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.410 AC: 27885 AN: 67960

Other (OTH) AF: 0.425 AC: 899 AN: 2114

Alfa AF: 0.403 Hom.: 55619

Bravo AF: 0.395

Asia WGS AF: 0.139 AC: 482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.26
DANN	Benign	0.29
PhyloP100		-0.79
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: rs10181042; hg19: chr2-61224259;