1-42682630-C-T

Variant names:

• chr1-42682630-C-T
• rs1650063130
• NM_004559.5:c.65C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_004559.5(YBX1):​c.65C>T​(p.Ala22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 1,256,508 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.000018 (0 hom.)
• Consequence: YBX1 NM_004559.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11670664).
• BS2: High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBX1	NM_004559.5	c.65C>T	p.Ala22Val	missense_variant	Exon 1 of 8	ENST00000321358.12	NP_004550.2
YBX1	XM_047421495.1	c.65C>T	p.Ala22Val	missense_variant	Exon 1 of 6		XP_047277451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YBX1	ENST00000321358.12	c.65C>T	p.Ala22Val	missense_variant	Exon 1 of 8	1	NM_004559.5	ENSP00000361626.3
YBX1	ENST00000332220.10	c.65C>T	p.Ala22Val	missense_variant	Exon 1 of 5	5		ENSP00000405937.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000183 AC: 23 AN: 1256508 Hom.: 0 Cov.: 32 AF XY: 0.0000130 AC XY: 8 AN XY: 617000

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000157

Gnomad4 OTH exome AF: 0.0000970

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.65C>T (p.A22V) alteration is located in exon 1 (coding exon 1) of the YBX1 gene. This alteration results from a C to T substitution at nucleotide position 65, causing the alanine (A) at amino acid position 22 to be replaced by a valine (V). 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	0.27
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.62	N;N
REVEL	Benign	0.062
Sift	Benign	0.045	D;T
Sift4G	Benign	0.12	T;T
Polyphen		0.0010	B;.
Vest4		0.35
MutPred		0.13		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.14
MPC		2.1
ClinPred		0.40	T
GERP RS		3.2
Varity_R		0.11
gMVP		0.29

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

Other links and lift over

dbSNP: rs1650063130; hg19: chr1-43148301;