X-7105790-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_012080.5(PUDP):c.110A>C(p.Tyr37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,207,104 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000065 (0 hom. 24 hem.)
• Consequence: PUDP NM_012080.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.76

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08127707).
• BS2: High Hemizygotes in GnomAdExome at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUDP	NM_012080.5	c.110A>C	p.Tyr37Ser	missense_variant	2/4	ENST00000381077.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUDP	ENST00000381077.10	c.110A>C	p.Tyr37Ser	missense_variant	2/4	1	NM_012080.5	P1

Frequencies

GnomAD3 genomes AF: 0.000108 AC: 12 AN: 111488 Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1 AN XY: 33690

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000191

Gnomad ASJ AF: 0.00302

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000377

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000134 AC: 24 AN: 179257 Hom.: 0 AF XY: 0.000199 AC XY: 13 AN XY: 65351

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000737

Gnomad ASJ exome AF: 0.00283

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000226

GnomAD4 exome AF: 0.0000648 AC: 71 AN: 1095616 Hom.: 0 Cov.: 29 AF XY: 0.0000665 AC XY: 24 AN XY: 361108

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000114

Gnomad4 ASJ exome AF: 0.00269

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000952

Gnomad4 OTH exome AF: 0.000152

GnomAD4 genome AF: 0.000108 AC: 12 AN: 111488 Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1 AN XY: 33690

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000191

Gnomad4 ASJ AF: 0.00302

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000377

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000436 Hom.: 5

Bravo AF: 0.000147

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000156 AC: 1

ExAC AF: 0.000149 AC: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2022

The c.179A>C (p.Y60S) alteration is located in exon 3 (coding exon 3) of the PUDP gene. This alteration results from a A to C substitution at nucleotide position 179, causing the tyrosine (Y) at amino acid position 60 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	22
Dann	Benign	0.97
DEOGEN2	Benign	0.16	T;.;.;.;.
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.081	T;T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Pathogenic	3.4	M;M;.;M;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-7.8	D;D;D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;.
Polyphen		1.0	D;D;.;D;P
Vest4		0.43
MVP		0.072
MPC		0.45
ClinPred		0.87	D
GERP RS		1.2
Varity_R		0.98
gMVP		0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs374501713; hg19: chrX-7023831;