NM_012080.5:c.28C>G

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_012080.5(PUDP):c.28C>G(p.His10Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000529 in 1,135,172 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000049 ( 0 hom. 2 hem. )

Consequence

PUDP
NM_012080.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65

Variant links:

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]

PUDP links:

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]

STS links:

MIR4767 (HGNC:41548): (microRNA 4767) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR4767 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PUDP	NM_012080.5 link	c.28C>G	p.His10Asp	missense_variant	Exon 1 of 4	ENST00000381077.10	NP_036212.3	Q08623-1
STS	NM_001320752.2 link	c.-134+3G>C		splice_region_variant, intron_variant	Intron 1 of 10	ENST00000674429.1	NP_001307681.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUDP	ENST00000381077.10 link	c.28C>G	p.His10Asp	missense_variant	Exon 1 of 4	1	NM_012080.5	ENSP00000370467.6		Q08623-1
STS	ENST00000674429.1 link	c.-134+3G>C		splice_region_variant, intron_variant	Intron 1 of 10		NM_001320752.2	ENSP00000501534.1		A0A590UJL0

Frequencies

GnomAD3 genomes

AF:

0.00000903

AC:

AN:

110790

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

33186

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000190

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

90823

Hom.:

AF XY:

0.0000339

AC XY:

AN XY:

29465

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000400

GnomAD4 exome

AF:

0.00000488

AC:

AN:

1024382

Hom.:

Cov.:

AF XY:

0.00000606

AC XY:

AN XY:

330192

show subpopulations

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:

0.00000622

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000903

AC:

AN:

110790

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

33186

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000190

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.28C>G (p.H10D) alteration is located in exon 1 (coding exon 1) of the PUDP gene. This alteration results from a C to G substitution at nucleotide position 28, causing the histidine (H) at amino acid position 10 to be replaced by an aspartic acid (D). 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

0.92

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.27

T;.;.;.;.

FATHMM_MKL

Benign

0.40

LIST_S2

Uncertain

0.92

D;D;D;D;D

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.63

D;D;D;D;D

MetaSVM

Benign

-0.78

MutationAssessor

Pathogenic

3.2

M;M;M;M;.

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-7.3

D;D;D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0030

D;D;D;D;D

Sift4G

Uncertain

0.010

D;D;D;D;.

Polyphen

0.97

D;D;.;D;D

Vest4

0.66

MutPred

0.55

Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.18

MPC

0.10

ClinPred

0.88

GERP RS

2.5

Varity_R

0.98

gMVP

0.91

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over