X-7077389-C-A

Variant names:

• chrX-7077389-C-A
• NM_012080.5:c.341G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_012080.5(PUDP):​c.341G>T​(p.Ser114Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,097,749 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: PUDP NM_012080.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.59
• Publications: 0 publications found

Genes affected

PUDP (HGNC:16818): (pseudouridine 5'-phosphatase) This gene encodes a member of the haloacid dehalogenase-like (HAD) hydrolase superfamily. The encoded protein has no known biological function. This gene has a pseudogene on chromosome 1. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.927

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012080.5. 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
	PUDP	NM_012080.5	MANE Select	c.341G>T	p.Ser114Ile	missense	Exon 3 of 4	NP_036212.3	Q08623-1
	PUDP	NM_001135565.2		c.410G>T	p.Ser137Ile	missense	Exon 4 of 5	NP_001129037.1	Q08623-4
	PUDP	NM_001178135.2		c.341G>T	p.Ser114Ile	missense	Exon 3 of 4	NP_001171606.1	Q08623-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUDP	ENST00000381077.10	TSL:1 MANE Select	c.341G>T	p.Ser114Ile	missense	Exon 3 of 4	ENSP00000370467.6	Q08623-1
	PUDP	ENST00000424830.6	TSL:3	c.410G>T	p.Ser137Ile	missense	Exon 4 of 5	ENSP00000396452.2	Q08623-4
	PUDP	ENST00000934726.1		c.341G>T	p.Ser114Ile	missense	Exon 3 of 4	ENSP00000604785.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097749 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 363189

African (AFR) AF: 0.0000379 AC: 1 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 35188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19381

East Asian (EAS) AF: 0.00 AC: 0 AN: 30195

South Asian (SAS) AF: 0.00 AC: 0 AN: 54097

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40497

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841787

Other (OTH) AF: 0.00 AC: 0 AN: 46065

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.086	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Pathogenic	4.8	H
PhyloP100		6.6
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.81		Loss of disorder (P = 0.003)
MVP		0.055
MPC		0.43
ClinPred		0.99	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.98
gMVP		0.89
Mutation Taster		=26/74	disease causing

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

hg19: chrX-6995430;