rs770325223

Variant names:

• chr2-60948093-C-G
• rs770325223
• NM_144709.4:c.1401G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-60948093-C-G
• chr2-60948093-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_144709.4(PUS10):​c.1401G>C​(p.Gln467His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PUS10 NM_144709.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.966
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09048119).
• BP6: Variant 2-60948093-C-G is Benign according to our data. Variant chr2-60948093-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2472127.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1401G>C	p.Gln467His	missense	Exon 16 of 18	NP_653310.2	Q3MIT2
	PUS10	NM_001322123.1		c.1401G>C	p.Gln467His	missense	Exon 16 of 18	NP_001309052.1	Q3MIT2
	PUS10	NM_001322124.1		c.1401G>C	p.Gln467His	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.1401G>C	p.Gln467His	missense	Exon 16 of 18	ENSP00000326003.6	Q3MIT2
	PUS10	ENST00000602599.1	TSL:1	n.4004G>C		non_coding_transcript_exon	Exon 14 of 16
	PUS10	ENST00000971235.1		c.1425G>C	p.Gln475His	missense	Exon 17 of 19	ENSP00000641294.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251470 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461852 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	10
DANN	Benign	0.44
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	-0.10	N
PhyloP100		0.97
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.20
Sift	Benign	0.34	T
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.096
MutPred		0.35		Gain of sheet (P = 0.0827)
MVP		0.59
MPC		0.037
ClinPred		0.10	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.32
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs770325223; hg19: chr2-61175228;