chr2-60943910-A-G

Variant names:

• chr2-60943910-A-G
• rs6706689
• NM_144709.4:c.1551+1099T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-1.0).
• 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 rank	MANE	Protein	UniProt
PUS10	NM_144709.4	c.1551+1099T>C		intron_variant	Intron 17 of 17	ENST00000316752.11	NP_653310.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUS10	ENST00000316752.11	c.1551+1099T>C		intron_variant	Intron 17 of 17	1	NM_144709.4	ENSP00000326003.6
PUS10	ENST00000602599.1	n.4154+1099T>C		intron_variant	Intron 15 of 15	1
PUS10	ENST00000407787.6	c.1551+1099T>C		intron_variant	Intron 17 of 17	2		ENSP00000386074.1
PUS10	ENST00000718444.1	n.5219+1099T>C		intron_variant	Intron 5 of 5

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

African (AFR) AF: 0.316 AC: 13030 AN: 41220

American (AMR) AF: 0.411 AC: 6252 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2079 AN: 3462

East Asian (EAS) AF: 0.0478 AC: 247 AN: 5168

South Asian (SAS) AF: 0.218 AC: 1045 AN: 4804

European-Finnish (FIN) AF: 0.617 AC: 6461 AN: 10472

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40934 AN: 67898

Other (OTH) AF: 0.520 AC: 1092 AN: 2098

Alfa AF: 0.569 Hom.: 38361

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
PhyloP100		-0.27
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: rs6706689; hg19: chr2-61171045;