2-60990407-T-C

Position:

• chr2-60990407-T-C

Variant summary

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

The NM_144709.4(PUS10):​c.468+16150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,004 control chromosomes in the GnomAD database, including 28,657 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 0.58 (28657 hom., cov: 31)
• Consequence: PUS10 NM_144709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUS10	NM_144709.4	c.468+16150A>G		intron_variant		ENST00000316752.11	NP_653310.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PUS10	ENST00000316752.11	c.468+16150A>G		intron_variant		1	NM_144709.4	ENSP00000326003	P1
PUS10	ENST00000602599.1	n.735+16150A>G		intron_variant, non_coding_transcript_variant		1
PUS10	ENST00000407787.5	c.468+16150A>G		intron_variant		2		ENSP00000386074	P1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88110 AN: 151886 Hom.: 28613 Cov.: 31

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.0446

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.580 AC: 88202 AN: 152004 Hom.: 28657 Cov.: 31 AF XY: 0.569 AC XY: 42303 AN XY: 74292

Gnomad4 AFR AF: 0.851

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.0445

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.569

Alfa AF: 0.514 Hom.: 44446

Bravo AF: 0.581

Asia WGS AF: 0.177 AC: 615 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	0.46
DANN	Benign	0.43

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: rs10188217; hg19: chr2-61217542;