NM_012080.5:c.43A>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_012080.5(PUDP):c.43A>T(p.Met15Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,135,592 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 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. M15V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000091 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000036 ( 0 hom. 9 hem. )

Consequence

PUDP
NM_012080.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.127

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31513762).

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PUDP	NM_012080.5	MANE Select	c.43A>T	p.Met15Leu	missense	Exon 1 of 4	NP_036212.3	Q08623-1
STS	NM_001320752.2	MANE Select	c.-146T>A		5_prime_UTR	Exon 1 of 11	NP_001307681.2	A0A590UJL0
PUDP	NM_001135565.2		c.43A>T	p.Met15Leu	missense	Exon 1 of 5	NP_001129037.1	Q08623-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PUDP	ENST00000381077.10	TSL:1 MANE Select	c.43A>T	p.Met15Leu	missense	Exon 1 of 4	ENSP00000370467.6	Q08623-1
STS	ENST00000674429.1	MANE Select	c.-146T>A		5_prime_UTR	Exon 1 of 11	ENSP00000501534.1	A0A590UJL0
PUDP	ENST00000424830.6	TSL:3	c.43A>T	p.Met15Leu	missense	Exon 1 of 5	ENSP00000396452.2	Q08623-4

Frequencies

GnomAD3 genomes

AF:

0.00000908

AC:

AN:

110091

Hom.:

Cov.:

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:

0.0000191

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000324

AC:

AN:

92530

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000605

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000564

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000361

AC:

AN:

1025501

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

330227

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22160

American (AMR)

AF:

0.0000784

AC:

AN:

25512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17630

East Asian (EAS)

AF:

0.00

AC:

AN:

24108

South Asian (SAS)

AF:

0.00

AC:

AN:

47790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37063

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3977

European-Non Finnish (NFE)

AF:

0.0000435

AC:

AN:

804326

Other (OTH)

AF:

0.00

AC:

AN:

42935

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000908

AC:

AN:

110091

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32665

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30468

American (AMR)

AF:

0.00

AC:

AN:

10606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2626

East Asian (EAS)

AF:

0.00

AC:

AN:

3402

South Asian (SAS)

AF:

0.00

AC:

AN:

2586

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5704

Middle Eastern (MID)

AF:

0.00

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.0000191

AC:

AN:

52323

Other (OTH)

AF:

0.00

AC:

AN:

1488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.047

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.80

M_CAP

Benign

0.0090

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

-0.13

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.8

REVEL

Benign

0.13

Sift

Benign

0.15

Sift4G

Benign

0.33

Polyphen

0.0020

Vest4

0.19

MutPred

0.77

Loss of sheet (P = 0.1907)

MVP

0.47

MPC

0.062

ClinPred

0.068

GERP RS

-0.31

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.57

gMVP

0.50

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over