chr2-60990407-T-C

Variant names:

• chr2-60990407-T-C
• rs10188217
• NM_144709.4:c.468+16150A>G

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+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
• Publications: 32 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=-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 rank	MANE	Protein	UniProt
PUS10	NM_144709.4	c.468+16150A>G		intron_variant	Intron 4 of 17	ENST00000316752.11	NP_653310.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUS10	ENST00000316752.11	c.468+16150A>G		intron_variant	Intron 4 of 17	1	NM_144709.4	ENSP00000326003.6
PUS10	ENST00000602599.1	n.735+16150A>G		intron_variant	Intron 4 of 15	1
PUS10	ENST00000407787.6	c.468+16150A>G		intron_variant	Intron 4 of 17	2		ENSP00000386074.1

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

African (AFR) AF: 0.851 AC: 35295 AN: 41482

American (AMR) AF: 0.417 AC: 6371 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2082 AN: 3468

East Asian (EAS) AF: 0.0445 AC: 230 AN: 5170

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4814

European-Finnish (FIN) AF: 0.541 AC: 5696 AN: 10538

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35719 AN: 67944

Other (OTH) AF: 0.569 AC: 1202 AN: 2112

Alfa AF: 0.530 Hom.: 96857

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
PhyloP100		-0.86
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: rs10188217; hg19: chr2-61217542;