rs141479423

Variant names:

• chr12-10704090-G-A
• rs141479423
• NM_003651.5:c.839C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-10704090-G-A
• chr12-10704090-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003651.5(YBX3):​c.839C>T​(p.Pro280Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,614,122 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P280Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: YBX3 NM_003651.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09855685).

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.839C>T	p.Pro280Leu	missense	Exon 7 of 10	NP_003642.3
	YBX3	NM_001145426.2		c.632C>T	p.Pro211Leu	missense	Exon 6 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.839C>T	p.Pro280Leu	missense	Exon 7 of 10	ENSP00000228251.4	P16989-1
	YBX3	ENST00000279550.11	TSL:1	c.632C>T	p.Pro211Leu	missense	Exon 6 of 9	ENSP00000279550.7	P16989-2
	YBX3	ENST00000955210.1		c.839C>T	p.Pro280Leu	missense	Exon 7 of 12	ENSP00000625269.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000143 AC: 36 AN: 251478 AF XY: 0.000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000235 AC: 343 AN: 1461894 Hom.: 0 Cov.: 30 AF XY: 0.000221 AC XY: 161 AN XY: 727248

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000286 AC: 318 AN: 1112012

Other (OTH) AF: 0.000232 AC: 14 AN: 60396

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74432

African (AFR) AF: 0.0000722 AC: 3 AN: 41526

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000265 Hom.: 1

Bravo AF: 0.000113

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000189 AC: 23

EpiCase AF: 0.000327

EpiControl AF: 0.000296

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	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.035	D
Polyphen		0.046	B
Vest4		0.43
MVP		0.21
MPC		0.13
ClinPred		0.11	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.057
gMVP		0.28
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141479423; hg19: chr12-10856689; COSMIC: COSV54384991; COSMIC: COSV54384991;