1-207050976-G-T

Variant names:

• chr1-207050976-G-T
• rs549752987
• NM_018566.4:c.55C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018566.4(YOD1):​c.55C>A​(p.Pro19Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. P19L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: YOD1 NM_018566.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15030715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YOD1	NM_018566.4	c.55C>A	p.Pro19Thr	missense_variant	Exon 1 of 2	ENST00000315927.9	NP_061036.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YOD1	ENST00000315927.9	c.55C>A	p.Pro19Thr	missense_variant	Exon 1 of 2	1	NM_018566.4	ENSP00000326813.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1389440 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 683660

African (AFR) AF: 0.00 AC: 0 AN: 31362

American (AMR) AF: 0.00 AC: 0 AN: 34712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24940

East Asian (EAS) AF: 0.00 AC: 0 AN: 35946

South Asian (SAS) AF: 0.00 AC: 0 AN: 80722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5434

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072624

Other (OTH) AF: 0.00 AC: 0 AN: 57400

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.1
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.024
Sift	Uncertain	0.023	D
Sift4G	Benign	0.082	T
Polyphen		0.084	B
Vest4		0.32
MutPred		0.23		Gain of glycosylation at P19 (P = 0.0163);
MVP		0.38
MPC		0.48
ClinPred		0.34	T
GERP RS		2.6
PromoterAI		0.20	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.055
gMVP		0.54
Mutation Taster		=97/3	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

Publications

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Other links and lift over

dbSNP: rs549752987; hg19: chr1-207224321;