NM_012080.5:c.284C>T

Variant names:

• chrX-7077446-G-A
• rs961213796
• NM_012080.5:c.284C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_012080.5(PUDP):​c.284C>T​(p.Ala95Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000833 in 1,200,682 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.0000073 (0 hom. 3 hem.)
• Consequence: PUDP NM_012080.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.85
• Publications: 1 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.21852893).
• BP6: Variant X-7077446-G-A is Benign according to our data. Variant chrX-7077446-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3428399.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 3 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.284C>T	p.Ala95Val	missense	Exon 3 of 4	NP_036212.3	Q08623-1
	PUDP	NM_001135565.2		c.353C>T	p.Ala118Val	missense	Exon 4 of 5	NP_001129037.1	Q08623-4
	PUDP	NM_001178135.2		c.284C>T	p.Ala95Val	missense	Exon 3 of 4	NP_001171606.1	Q08623-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUDP	ENST00000381077.10	TSL:1 MANE Select	c.284C>T	p.Ala95Val	missense	Exon 3 of 4	ENSP00000370467.6	Q08623-1
	PUDP	ENST00000424830.6	TSL:3	c.353C>T	p.Ala118Val	missense	Exon 4 of 5	ENSP00000396452.2	Q08623-4
	PUDP	ENST00000934726.1		c.284C>T	p.Ala95Val	missense	Exon 3 of 4	ENSP00000604785.1

Frequencies

GnomAD3 genomes AF: 0.0000180 AC: 2 AN: 111155 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000327

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: 0.0000189

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000734 AC: 8 AN: 1089527 Hom.: 0 Cov.: 32 AF XY: 0.00000844 AC XY: 3 AN XY: 355521

African (AFR) AF: 0.00 AC: 0 AN: 26279

American (AMR) AF: 0.00 AC: 0 AN: 35093

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19311

East Asian (EAS) AF: 0.0000995 AC: 3 AN: 30147

South Asian (SAS) AF: 0.0000186 AC: 1 AN: 53686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40423

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4108

European-Non Finnish (NFE) AF: 0.00000479 AC: 4 AN: 834699

Other (OTH) AF: 0.00 AC: 0 AN: 45781

GnomAD4 genome AF: 0.0000180 AC: 2 AN: 111155 Hom.: 0 Cov.: 22 AF XY: 0.0000300 AC XY: 1 AN XY: 33347

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000327 AC: 1 AN: 30565

American (AMR) AF: 0.00 AC: 0 AN: 10451

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3519

South Asian (SAS) AF: 0.00 AC: 0 AN: 2606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5967

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 53007

Other (OTH) AF: 0.00 AC: 0 AN: 1480

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Likely benign

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	Benign	0.19
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.8
DANN	Benign	0.35
DEOGEN2	Benign	0.034	T
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.31	N
PhyloP100		3.8
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.18
Sift	Benign	0.53	T
Sift4G	Benign	0.79	T
Polyphen		0.24	B
Vest4		0.19
MutPred		0.70		Gain of methylation at K97 (P = 0.1102)
MVP		0.067
MPC		0.11
ClinPred		0.20	T
GERP RS		0.067
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.69
Mutation Taster		=79/21	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: rs961213796; hg19: chrX-6995487; COSMIC: COSV101127839;