Variant 17-7294332-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015982.4(YBX2):c.169A>T(p.Thr57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,154,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

YBX2
NM_015982.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.269

Variant links:

Genes affected

YBX2 (HGNC:17948): (Y-box binding protein 2) This gene encodes a nucleic acid binding protein which is highly expressed in germ cells. The encoded protein binds to a Y-box element in the promoters of certain genes but also binds to mRNA transcribed from these genes. Pseudogenes for this gene are located on chromosome 10 and 15. [provided by RefSeq, Feb 2012]

YBX2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08574098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YBX2	NM_015982.4 link	c.169A>T	p.Thr57Ser	missense_variant	Exon 1 of 9	ENST00000007699.10	NP_057066.2	Q9Y2T7A0A384MDP4
YBX2	XM_017024713.3 link	c.169A>T	p.Thr57Ser	missense_variant	Exon 1 of 10		XP_016880202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
YBX2	ENST00000007699.10 link	c.169A>T	p.Thr57Ser	missense_variant	Exon 1 of 9	1	NM_015982.4	ENSP00000007699.5	Q9Y2T7
YBX2	ENST00000571127.1 link	n.225A>T		non_coding_transcript_exon_variant	Exon 1 of 2	2
YBX2	ENST00000571485.5 link	n.258A>T		non_coding_transcript_exon_variant	Exon 1 of 6	2
YBX2	ENST00000570627.1 link	n.48+236A>T		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000147

AC:

AN:

6808

Hom.:

AF XY:

0.000219

AC XY:

AN XY:

4558

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000340

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000113

AC:

AN:

1154664

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

559272

show subpopulations

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:

0.0000261

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000103

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.169A>T (p.T57S) alteration is located in exon 1 (coding exon 1) of the YBX2 gene. This alteration results from a A to T substitution at nucleotide position 169, causing the threonine (T) at amino acid position 57 to be replaced by a serine (S). 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

0.092

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.044

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.25

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.60

REVEL

Benign

0.036

Sift

Benign

0.17

Sift4G

Benign

0.067

Polyphen

0.38

Vest4

0.24

MutPred

0.17

Gain of glycosylation at P58 (P = 0.0868);

MVP

0.043

MPC

1.2

ClinPred

0.046

GERP RS

2.4

Varity_R

0.054

gMVP

0.086

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over