X-7148092-C-A

Position:

• chrX-7148092-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012080.5(PUDP):​c.22G>T​(p.Val8Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: PUDP NM_012080.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.856

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]

STS (HGNC:11425): (steroid sulfatase) This gene encodes a multi-pass membrane protein that is localized to the endoplasmic reticulum. It belongs to the sulfatase family and hydrolyzes several 3-beta-hydroxysteroid sulfates, which serve as metabolic precursors for estrogens, androgens, and cholesterol. Mutations in this gene are associated with X-linked ichthyosis (XLI). Alternatively spliced transcript variants resulting from the use of different promoters have been described for this gene (PMID:17601726). [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2574464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUDP	NM_012080.5	c.22G>T	p.Val8Phe	missense_variant	1/4	ENST00000381077.10
STS	NM_001320752.2	c.-134+9C>A		intron_variant		ENST00000674429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUDP	ENST00000381077.10	c.22G>T	p.Val8Phe	missense_variant	1/4	1	NM_012080.5	P1
STS	ENST00000674429.1	c.-134+9C>A		intron_variant			NM_001320752.2	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1013448 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 325174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

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

Jan 31, 2024

The c.22G>T (p.V8F) alteration is located in exon 1 (coding exon 1) of the PUDP gene. This alteration results from a G to T substitution at nucleotide position 22, causing the valine (V) at amino acid position 8 to be replaced by a phenylalanine (F). 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	0.77
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;.;.;.;.
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.72	T;T;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;L;L;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.6	D;D;D;D;D
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;.
Polyphen		1.0	D;D;.;D;B
Vest4		0.43
MutPred		0.50		Gain of glycosylation at P7 (P = 0.1058);Gain of glycosylation at P7 (P = 0.1058);Gain of glycosylation at P7 (P = 0.1058);Gain of glycosylation at P7 (P = 0.1058);Gain of glycosylation at P7 (P = 0.1058);
MVP		0.11
MPC		0.39
ClinPred		0.95	D
GERP RS		1.6
Varity_R		0.72
gMVP		0.71

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: rs1569174011; hg19: chrX-7066133;