NM_012080.5:c.43A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012080.5(PUDP):c.43A>G(p.Met15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000973 in 1,135,641 control chromosomes in the GnomAD database, including 1 homozygotes. There are 337 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 0.00064 ( 0 hom., 23 hem., cov: 23)

Exomes 𝑓: 0.0010 ( 1 hom. 314 hem. )

Consequence

PUDP
NM_012080.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.127

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03861448).

BS2

High Hemizygotes in GnomAd4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PUDP	NM_012080.5 link	c.43A>G	p.Met15Val	missense_variant	Exon 1 of 4	ENST00000381077.10	NP_036212.3	Q08623-1
STS	NM_001320752.2 link	c.-146T>C		5_prime_UTR_variant	Exon 1 of 11	ENST00000674429.1	NP_001307681.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUDP	ENST00000381077.10 link	c.43A>G	p.Met15Val	missense_variant	Exon 1 of 4	1	NM_012080.5	ENSP00000370467.6		Q08623-1
STS	ENST00000674429 link	c.-146T>C		5_prime_UTR_variant	Exon 1 of 11		NM_001320752.2	ENSP00000501534.1		A0A590UJL0

Frequencies

GnomAD3 genomes

AF:

0.000636

AC:

AN:

110091

Hom.:

Cov.:

AF XY:

0.000704

AC XY:

AN XY:

32665

show subpopulations

Gnomad AFR

AF:

0.0000656

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000283

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00298

Gnomad MID

AF:

0.00435

Gnomad NFE

AF:

0.000879

Gnomad OTH

AF:

0.000672

GnomAD3 exomes

AF:

0.000724

AC:

AN:

92530

Hom.:

AF XY:

0.000969

AC XY:

AN XY:

29942

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000824

Gnomad FIN exome

AF:

0.00305

Gnomad NFE exome

AF:

0.000817

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00101

AC:

1035

AN:

1025498

Hom.:

Cov.:

AF XY:

0.000951

AC XY:

314

AN XY:

330224

show subpopulations

Gnomad4 AFR exome

AF:

0.000226

Gnomad4 AMR exome

AF:

0.000118

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000126

Gnomad4 FIN exome

AF:

0.00324

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.000792

GnomAD4 genome

AF:

0.000636

AC:

AN:

110143

Hom.:

Cov.:

AF XY:

0.000703

AC XY:

AN XY:

32725

show subpopulations

Gnomad4 AFR

AF:

0.0000655

Gnomad4 AMR

AF:

0.000283

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00298

Gnomad4 NFE

AF:

0.000879

Gnomad4 OTH

AF:

0.000663

Alfa

AF:

0.000256

Hom.:

Bravo

AF:

0.000495

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000593

AC:

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.43A>G (p.M15V) alteration is located in exon 1 (coding exon 1) of the PUDP gene. This alteration results from a A to G substitution at nucleotide position 43, causing the methionine (M) at amino acid position 15 to be replaced by a valine (V). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.13

T;.;.;.;.

FATHMM_MKL

Benign

0.20

LIST_S2

Uncertain

0.91

D;D;T;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.039

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;M;M;M;.

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Benign

0.13

Sift

Benign

0.034

D;T;D;D;D

Sift4G

Benign

0.11

T;T;T;D;.

Polyphen

0.12

B;B;.;B;B

Vest4

0.42

MVP

0.48

MPC

0.077

ClinPred

0.10

GERP RS

-0.31

Varity_R

0.65

gMVP

0.62

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