chr2-60948083-C-G

Variant names:

• chr2-60948083-C-G
• rs925807613
• NM_144709.4:c.1411G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144709.4(PUS10):​c.1411G>C​(p.Glu471Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E471K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PUS10 NM_144709.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.722
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2963014).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144709.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUS10	NM_144709.4	MANE Select	c.1411G>C	p.Glu471Gln	missense	Exon 16 of 18	NP_653310.2	Q3MIT2
	PUS10	NM_001322123.1		c.1411G>C	p.Glu471Gln	missense	Exon 16 of 18	NP_001309052.1	Q3MIT2
	PUS10	NM_001322124.1		c.1411G>C	p.Glu471Gln	missense	Exon 16 of 18	NP_001309053.1	A8K6R4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUS10	ENST00000316752.11	TSL:1 MANE Select	c.1411G>C	p.Glu471Gln	missense	Exon 16 of 18	ENSP00000326003.6	Q3MIT2
	PUS10	ENST00000602599.1	TSL:1	n.4014G>C		non_coding_transcript_exon	Exon 14 of 16
	PUS10	ENST00000971235.1		c.1435G>C	p.Glu479Gln	missense	Exon 17 of 19	ENSP00000641294.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	0.095
Eigen_PC	Benign	-0.011
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	0.49	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.72
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.80	N
REVEL	Uncertain	0.37
Sift	Benign	0.13	T
Sift4G	Benign	0.50	T
Polyphen		0.97	D
Vest4		0.18
MutPred		0.44		Gain of sheet (P = 0.0827)
MVP		0.87
MPC		0.039
ClinPred		0.49	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
gMVP		0.40
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs925807613; hg19: chr2-61175218;