NM_012080.5:c.43A>G

Variant names:

• chrX-7148071-T-C
• rs374016250
• NM_012080.5:c.43A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.127
• Publications: 2 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03861448).
• BS2: High Hemizygotes in GnomAd4 at 23 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUDP	NM_012080.5	MANE Select	c.43A>G	p.Met15Val	missense	Exon 1 of 4	NP_036212.3	Q08623-1
	STS	NM_001320752.2	MANE Select	c.-146T>C		5_prime_UTR	Exon 1 of 11	NP_001307681.2	A0A590UJL0
	PUDP	NM_001135565.2		c.43A>G	p.Met15Val	missense	Exon 1 of 5	NP_001129037.1	Q08623-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUDP	ENST00000381077.10	TSL:1 MANE Select	c.43A>G	p.Met15Val	missense	Exon 1 of 4	ENSP00000370467.6	Q08623-1
	STS	ENST00000674429.1	MANE Select	c.-146T>C		5_prime_UTR	Exon 1 of 11	ENSP00000501534.1	A0A590UJL0
	PUDP	ENST00000424830.6	TSL:3	c.43A>G	p.Met15Val	missense	Exon 1 of 5	ENSP00000396452.2	Q08623-4

Frequencies

GnomAD3 genomes AF: 0.000636 AC: 70 AN: 110091 Hom.: 0 Cov.: 23

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

GnomAD2 exomes AF: 0.000724 AC: 67 AN: 92530 AF XY: 0.000969

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 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.: 1 Cov.: 28 AF XY: 0.000951 AC XY: 314 AN XY: 330224

African (AFR) AF: 0.000226 AC: 5 AN: 22159

American (AMR) AF: 0.000118 AC: 3 AN: 25511

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17630

East Asian (EAS) AF: 0.00 AC: 0 AN: 24108

South Asian (SAS) AF: 0.000126 AC: 6 AN: 47790

European-Finnish (FIN) AF: 0.00324 AC: 120 AN: 37063

Middle Eastern (MID) AF: 0.000503 AC: 2 AN: 3977

European-Non Finnish (NFE) AF: 0.00108 AC: 865 AN: 804325

Other (OTH) AF: 0.000792 AC: 34 AN: 42935

GnomAD4 genome AF: 0.000636 AC: 70 AN: 110143 Hom.: 0 Cov.: 23 AF XY: 0.000703 AC XY: 23 AN XY: 32725

African (AFR) AF: 0.0000655 AC: 2 AN: 30533

American (AMR) AF: 0.000283 AC: 3 AN: 10619

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2626

East Asian (EAS) AF: 0.00 AC: 0 AN: 3390

South Asian (SAS) AF: 0.00 AC: 0 AN: 2580

European-Finnish (FIN) AF: 0.00298 AC: 17 AN: 5704

Middle Eastern (MID) AF: 0.00478 AC: 1 AN: 209

European-Non Finnish (NFE) AF: 0.000879 AC: 46 AN: 52316

Other (OTH) AF: 0.000663 AC: 1 AN: 1508

Alfa AF: 0.000256 Hom.: 3

Bravo AF: 0.000495

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000593 AC: 3

ExAC AF: 0.000157 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Benign	0.20	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.13
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.13
Sift	Benign	0.034	D
Sift4G	Benign	0.11	T
Polyphen		0.12	B
Vest4		0.42
MVP		0.48
MPC		0.077
ClinPred		0.10	T
GERP RS		-0.31
PromoterAI		0.031	Neutral
Varity_R		0.65
gMVP		0.62
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs374016250; hg19: chrX-7066112;