NM_004559.5:c.58C>T

Variant names:

• chr1-42682623-C-T
• rs1303277735
• NM_004559.5:c.58C>T

Variant summary

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

The NM_004559.5(YBX1):​c.58C>T​(p.Leu20Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000071 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: YBX1 NM_004559.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.269
• Publications: 2 publications found

Genes affected

YBX1 (HGNC:8014): (Y-box binding protein 1) This gene encodes a highly conserved cold shock domain protein that has broad nucleic acid binding properties. The encoded protein functions as both a DNA and RNA binding protein and has been implicated in numerous cellular processes including regulation of transcription and translation, pre-mRNA splicing, DNA reparation and mRNA packaging. This protein is also a component of messenger ribonucleoprotein (mRNP) complexes and may have a role in microRNA processing. This protein can be secreted through non-classical pathways and functions as an extracellular mitogen. Aberrant expression of the gene is associated with cancer proliferation in numerous tissues. This gene may be a prognostic marker for poor outcome and drug resistance in certain cancers. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on multiple chromosomes. [provided by RefSeq, Sep 2015]

ENSG00000285728 (HGNC:):

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=0.12596142).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004559.5. 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
	YBX1	NM_004559.5	MANE Select	c.58C>T	p.Leu20Phe	missense	Exon 1 of 8	NP_004550.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YBX1	ENST00000321358.12	TSL:1 MANE Select	c.58C>T	p.Leu20Phe	missense	Exon 1 of 8	ENSP00000361626.3	P67809
	YBX1	ENST00000936897.1		c.58C>T	p.Leu20Phe	missense	Exon 1 of 9	ENSP00000606956.1
	YBX1	ENST00000886270.1		c.58C>T	p.Leu20Phe	missense	Exon 1 of 8	ENSP00000556329.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000708 AC: 9 AN: 1271620 Hom.: 0 Cov.: 32 AF XY: 0.00000800 AC XY: 5 AN XY: 624874

African (AFR) AF: 0.00 AC: 0 AN: 25424

American (AMR) AF: 0.00 AC: 0 AN: 20686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20042

East Asian (EAS) AF: 0.00 AC: 0 AN: 27590

South Asian (SAS) AF: 0.00 AC: 0 AN: 64908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30652

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3662

European-Non Finnish (NFE) AF: 0.00000877 AC: 9 AN: 1026394

Other (OTH) AF: 0.00 AC: 0 AN: 52262

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.22
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.27
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.059
Sift	Benign	0.043	D
Sift4G	Benign	0.53	T
Polyphen		0.028	B
Vest4		0.18
MutPred		0.080		Loss of helix (P = 0.1299)
MVP		0.14
MPC		2.0
ClinPred		0.39	T
GERP RS		3.2
PromoterAI		-0.048	Neutral
Varity_R		0.15
gMVP		0.065
Mutation Taster		=91/9	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: rs1303277735; hg19: chr1-43148294;