12-10701994-C-G

Variant names:

• chr12-10701994-C-G
• rs184471157
• NM_003651.5:c.1019G>C

Variant summary

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

The NM_003651.5(YBX3):​c.1019G>C​(p.Arg340Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,470 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R340H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: YBX3 NM_003651.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.42
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1019G>C	p.Arg340Pro	missense	Exon 8 of 10	NP_003642.3
	YBX3	NM_001145426.2		c.812G>C	p.Arg271Pro	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.1019G>C	p.Arg340Pro	missense	Exon 8 of 10	ENSP00000228251.4	P16989-1
	YBX3	ENST00000279550.11	TSL:1	c.812G>C	p.Arg271Pro	missense	Exon 7 of 9	ENSP00000279550.7	P16989-2
	YBX3	ENST00000955210.1		c.1214G>C	p.Arg405Pro	missense	Exon 10 of 12	ENSP00000625269.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461470 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727048

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111872

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.0078	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		3.4
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.035	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.46		Gain of catalytic residue at P339 (P = 0)
MVP		0.40
MPC		0.72
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.47
gMVP		0.35
Mutation Taster		=78/22	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: rs184471157; hg19: chr12-10854593;