rs1361843119

Variant names:

• chr2-60965074-G-A
• NM_144709.4:c.707C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-60965074-G-A
• chr2-60965074-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144709.4(PUS10):​c.707C>T​(p.Pro236Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,462 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PUS10 NM_144709.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.93

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PUS10	NM_144709.4	c.707C>T	p.Pro236Leu	missense_variant	Exon 8 of 18	ENST00000316752.11	NP_653310.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUS10	ENST00000316752.11	c.707C>T	p.Pro236Leu	missense_variant	Exon 8 of 18	1	NM_144709.4	ENSP00000326003.6
PUS10	ENST00000602599.1	n.3310C>T		non_coding_transcript_exon_variant	Exon 6 of 16	1
PUS10	ENST00000407787.5	c.707C>T	p.Pro236Leu	missense_variant	Exon 8 of 18	2		ENSP00000386074.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461462 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727028

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Uncertain	0.54
Sift	Benign	0.24	T;T
Sift4G	Benign	0.67	T;T
Polyphen		0.97	D;D
Vest4		0.42
MutPred		0.44		Gain of helix (P = 0.0093);Gain of helix (P = 0.0093);
MVP		0.67
MPC		0.21
ClinPred		0.99	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.44		Position offset: -16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-61192209;