1-207050976-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018566.4(YOD1):c.55C>T(p.Pro19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000214 in 1,541,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P19L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000052 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

YOD1
NM_018566.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

Variant links:

Genes affected

YOD1 (HGNC:25035): (YOD1 deubiquitinase) Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. The protein encoded by this gene belongs to a DUB subfamily characterized by an ovarian tumor (OTU) domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

YOD1 links:

PFKFB2 (HGNC:8873): (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2) The protein encoded by this gene is involved in both the synthesis and degradation of fructose-2,6-bisphosphate, a regulatory molecule that controls glycolysis in eukaryotes. The encoded protein has a 6-phosphofructo-2-kinase activity that catalyzes the synthesis of fructose-2,6-bisphosphate, and a fructose-2,6-biphosphatase activity that catalyzes the degradation of fructose-2,6-bisphosphate. This protein regulates fructose-2,6-bisphosphate levels in the heart, while a related enzyme encoded by a different gene regulates fructose-2,6-bisphosphate levels in the liver and muscle. This enzyme functions as a homodimer. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PFKFB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008466423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YOD1	NM_018566.4 link	c.55C>T	p.Pro19Ser	missense_variant	Exon 1 of 2	ENST00000315927.9	NP_061036.3	Q5VVQ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YOD1	ENST00000315927.9 link	c.55C>T	p.Pro19Ser	missense_variant	Exon 1 of 2	1	NM_018566.4	ENSP00000326813.4		Q5VVQ6-1

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152268

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:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000119

AC:

AN:

151052

AF XY:

0.000109

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00166

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000180

AC:

AN:

1389442

Hom.:

Cov.:

AF XY:

0.0000146

AC XY:

AN XY:

683660

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31362

American (AMR)

AF:

0.00

AC:

AN:

34712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24940

East Asian (EAS)

AF:

0.000473

AC:

AN:

35946

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5434

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1072626

Other (OTH)

AF:

0.000122

AC:

AN:

57400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152386

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41600

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000272

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 27, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.55C>T (p.P19S) alteration is located in exon 1 (coding exon 1) of the YOD1 gene. This alteration results from a C to T substitution at nucleotide position 55, causing the proline (P) at amino acid position 19 to be replaced by a serine (S). 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

Benign

0.073

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.013

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.50

M_CAP

Benign

0.0070

MetaRNN

Benign

0.0085

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

PhyloP100

2.1

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.070

REVEL

Benign

0.021

Sift

Benign

0.28

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.19

MutPred

0.26

Gain of glycosylation at P19 (P = 0.0057);

MVP

0.26

MPC

0.41

ClinPred

0.085

GERP RS

2.6

PromoterAI

0.20

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.034

gMVP

0.52

Mutation Taster

=97/3

polymorphism

(source)

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

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1-207050976-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over