12-10702059-A-T

Variant names:

• chr12-10702059-A-T
• NM_003651.5:c.954T>A
• YBX3 p.Ser318Arg

Variant summary

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

The NM_003651.5(YBX3):​c.954T>A​(p.Ser318Arg) 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. 14/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: YBX3 NM_003651.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• Publications: 0 publications found

Genes affected

YBX3 (HGNC:2428): (Y-box binding protein 3) Enables RNA binding activity. Involved in cellular hyperosmotic response; cellular response to tumor necrosis factor; and negative regulation of programmed cell death. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09503123).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003651.5. 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
	YBX3	NM_003651.5	MANE Select	c.954T>A	p.Ser318Arg	missense	Exon 8 of 10	NP_003642.3
	YBX3	NM_001145426.2		c.747T>A	p.Ser249Arg	missense	Exon 7 of 9	NP_001138898.1	P16989-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YBX3	ENST00000228251.9	TSL:1 MANE Select	c.954T>A	p.Ser318Arg	missense	Exon 8 of 10	ENSP00000228251.4	P16989-1
	YBX3	ENST00000279550.11	TSL:1	c.747T>A	p.Ser249Arg	missense	Exon 7 of 9	ENSP00000279550.7	P16989-2
	YBX3	ENST00000955210.1		c.1149T>A	p.Ser383Arg	missense	Exon 10 of 12	ENSP00000625269.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.22
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.038
Sift	Benign	0.039	D
Sift4G	Benign	0.45	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.072
gMVP		0.23
Mutation Taster		=90/10	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-10854658;