rs6706689

chr2-60943910-A-G

Variant summary

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

The NM_144709.4(PUS10):c.1551+1099T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,542 control chromosomes in the GnomAD database, including 19,023 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 0.47 (19023 hom., cov: 29)
• Consequence: PUS10 NM_144709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUS10	NM_144709.4	c.1551+1099T>C		intron_variant		ENST00000316752.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUS10	ENST00000316752.11	c.1551+1099T>C		intron_variant		1	NM_144709.4	P1
PUS10	ENST00000602599.1	n.4154+1099T>C		intron_variant, non_coding_transcript_variant		1
PUS10	ENST00000407787.5	c.1551+1099T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71845 AN: 151424 Hom.: 19025 Cov.: 29

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.0477

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.474 AC: 71864 AN: 151542 Hom.: 19023 Cov.: 29 AF XY: 0.466 AC XY: 34514 AN XY: 74032

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.0478

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.520

Alfa AF: 0.571 Hom.: 32521

Bravo AF: 0.453

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	6.9
Dann	Benign	0.55

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: rs6706689; hg19: chr2-61171045;