Genetic Variant YOD1:c.*5006A>G (chr1-207044014-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018566.4(YOD1):c.*5006A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,426 control chromosomes in the GnomAD database, including 30,033 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.61 ( 29982 hom., cov: 32)

Exomes 𝑓: 0.48 ( 51 hom. )

Consequence

YOD1
NM_018566.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YOD1	NM_018566.4 link	c.*5006A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000315927.9	NP_061036.3	Q5VVQ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YOD1	ENST00000315927 link	c.*5006A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_018566.4	ENSP00000326813.4		Q5VVQ6-1

Frequencies

GnomAD3 genomes

AF:

0.611

AC:

92753

AN:

151900

Hom.:

29938

Cov.:

show subpopulations

Gnomad AFR

AF:

0.814

Gnomad AMI

AF:

0.484

Gnomad AMR

AF:

0.560

Gnomad ASJ

AF:

0.645

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.547

Gnomad OTH

AF:

0.634

GnomAD4 exome

AF:

0.483

AC:

197

AN:

408

Hom.:

Cov.:

AF XY:

0.463

AC XY:

114

AN XY:

246

show subpopulations

Gnomad4 FIN exome

AF:

0.483

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.611

AC:

92856

AN:

152018

Hom.:

29982

Cov.:

AF XY:

0.605

AC XY:

44957

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.814

Gnomad4 AMR

AF:

0.559

Gnomad4 ASJ

AF:

0.645

Gnomad4 EAS

AF:

0.247

Gnomad4 SAS

AF:

0.393

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.547

Gnomad4 OTH

AF:

0.633

Alfa

AF:

0.566

Hom.:

10658

Bravo

AF:

0.621

Asia WGS

AF:

0.347

AC:

1209

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.79

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over