chrX-7077347-T-C

Variant names:

• chrX-7077347-T-C
• rs1010251961
• NM_012080.5:c.383A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012080.5(PUDP):​c.383A>G​(p.Lys128Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,409 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 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. K128T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: PUDP NM_012080.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.987
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09905517).

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.383A>G	p.Lys128Arg	missense	Exon 3 of 4	NP_036212.3	Q08623-1
	PUDP	NM_001135565.2		c.452A>G	p.Lys151Arg	missense	Exon 4 of 5	NP_001129037.1	Q08623-4
	PUDP	NM_001178135.2		c.383A>G	p.Lys128Arg	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.383A>G	p.Lys128Arg	missense	Exon 3 of 4	ENSP00000370467.6	Q08623-1
	PUDP	ENST00000424830.6	TSL:3	c.452A>G	p.Lys151Arg	missense	Exon 4 of 5	ENSP00000396452.2	Q08623-4
	PUDP	ENST00000934726.1		c.383A>G	p.Lys128Arg	missense	Exon 3 of 4	ENSP00000604785.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097409 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 362865

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.00 AC: 0 AN: 35139

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30169

South Asian (SAS) AF: 0.00 AC: 0 AN: 54039

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841703

Other (OTH) AF: 0.00 AC: 0 AN: 46043

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.74
DEOGEN2	Benign	0.034	T
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.99
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.048
Sift	Benign	0.54	T
Sift4G	Benign	0.50	T
Polyphen		0.0010	B
Vest4		0.050
MutPred		0.46		Loss of ubiquitination at K128 (P = 0.0167)
MVP		0.12
MPC		0.057
ClinPred		0.11	T
GERP RS		2.7
Varity_R		0.12
gMVP		0.39
Mutation Taster		=87/13	polymorphism

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: rs1010251961; hg19: chrX-6995388;