2-60959694-A-G

Position:

• chr2-60959694-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.1000+698T>C 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 152,088 control chromosomes in the GnomAD database, including 21,716 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 0.49 (21716 hom., cov: 32)
• Consequence: PUS10 NM_144709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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]

PUS10 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUS10	NM_144709.4	c.1000+698T>C		intron_variant		ENST00000316752.11	NP_653310.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PUS10	ENST00000316752.11	c.1000+698T>C		intron_variant		1	NM_144709.4	ENSP00000326003.6
PUS10	ENST00000602599.1	n.3603+698T>C		intron_variant		1
PUS10	ENST00000407787.5	c.1000+698T>C		intron_variant		2		ENSP00000386074.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73701 AN: 151968 Hom.: 21667 Cov.: 32

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.0341

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.485 AC: 73802 AN: 152088 Hom.: 21716 Cov.: 32 AF XY: 0.475 AC XY: 35295 AN XY: 74340

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.0341

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.468

Alfa AF: 0.390 Hom.: 27806

Bravo AF: 0.497

Asia WGS AF: 0.155 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.8
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs13003464; hg19: chr2-61186829;