Variant 11-119420159-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006288.5(THY1):c.265C>T(p.Leu89Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000539 in 1,614,266 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: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

THY1
NM_006288.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

Variant links:

Genes affected

THY1 (HGNC:11801): (Thy-1 cell surface antigen) This gene encodes a cell surface glycoprotein and member of the immunoglobulin superfamily of proteins. The encoded protein is involved in cell adhesion and cell communication in numerous cell types, but particularly in cells of the immune and nervous systems. The encoded protein is widely used as a marker for hematopoietic stem cells. This gene may function as a tumor suppressor in nasopharyngeal carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

THY1 links:

USP2-AS1 (HGNC:48673): (USP2 antisense RNA 1)

USP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4097357).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THY1	NM_006288.5 link	c.265C>T	p.Leu89Phe	missense_variant	3/4	ENST00000284240.10	NP_006279.2	P04216B0YJA4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THY1	ENST00000284240.10 link	c.265C>T	p.Leu89Phe	missense_variant	3/4	1	NM_006288.5	ENSP00000284240.6		P04216

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000107

AC:

AN:

251496

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

135922

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:

0.000882

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000561

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

727248

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:

0.000904

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152372

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.265C>T (p.L89F) alteration is located in exon 3 (coding exon 2) of the THY1 gene. This alteration results from a C to T substitution at nucleotide position 265, causing the leucine (L) at amino acid position 89 to be replaced by a phenylalanine (F). 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

Pathogenic

0.71

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T;T;T;T

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

.;T;T;T;T

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.41

T;T;T;T;T

MetaSVM

Uncertain

0.16

MutationAssessor

Uncertain

2.7

M;M;.;.;.

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.1

D;D;D;.;D

REVEL

Pathogenic

0.76

Sift

Pathogenic

0.0

D;D;D;.;D

Sift4G

Pathogenic

0.0

D;D;.;D;.

Polyphen

1.0

D;D;.;.;.

Vest4

0.84

MutPred

0.73

Loss of MoRF binding (P = 0.1344);Loss of MoRF binding (P = 0.1344);Loss of MoRF binding (P = 0.1344);.;Loss of MoRF binding (P = 0.1344);

MVP

0.91

MPC

1.3

ClinPred

0.54

GERP RS

4.8

Varity_R

0.76

gMVP

0.88

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