rs7608910

chr2-60977721-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.469-6164T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,058 control chromosomes in the GnomAD database, including 10,557 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 0.36 (10557 hom., cov: 31)
• Consequence: PUS10 NM_144709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254

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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUS10	NM_144709.4	c.469-6164T>C		intron_variant		ENST00000316752.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUS10	ENST00000316752.11	c.469-6164T>C		intron_variant		1	NM_144709.4	P1
PUS10	ENST00000602599.1	n.736-6164T>C		intron_variant, non_coding_transcript_variant		1
PUS10	ENST00000407787.5	c.469-6164T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55180 AN: 151940 Hom.: 10546 Cov.: 31

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.363 AC: 55234 AN: 152058 Hom.: 10557 Cov.: 31 AF XY: 0.356 AC XY: 26492 AN XY: 74316

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.0396

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.384

Alfa AF: 0.372 Hom.: 13855

Bravo AF: 0.360

Asia WGS AF: 0.127 AC: 443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	14
Dann	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7608910; hg19: chr2-61204856;