Variant 11-119419461-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006288.5(THY1):c.433C>G(p.Leu145Val) 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 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

THY1
NM_006288.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THY1	NM_006288.5 linkuse as main transcript	c.433C>G	p.Leu145Val	missense_variant	4/4	ENST00000284240.10	NP_006279.2
USP2-AS1	NR_034160.1 linkuse as main transcript	n.305+24307G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THY1	ENST00000284240.10 linkuse as main transcript	c.433C>G	p.Leu145Val	missense_variant	4/4	1	NM_006288.5	ENSP00000284240	P1
USP2-AS1	ENST00000706409.1 linkuse as main transcript	n.252-50348G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461648

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727134

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

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

Jul 30, 2023

The c.433C>G (p.L145V) alteration is located in exon 4 (coding exon 3) of the THY1 gene. This alteration results from a C to G substitution at nucleotide position 433, causing the leucine (L) at amino acid position 145 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

T;T;T;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.83

.;T;T;T

M_CAP

Uncertain

0.087

MetaRNN

Uncertain

0.46

T;T;T;T

MetaSVM

Uncertain

0.076

MutationAssessor

Uncertain

2.0

M;M;.;.

MutationTaster

Benign

0.66

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.2

N;N;.;N

REVEL

Uncertain

0.59

Sift

Uncertain

0.022

D;D;.;D

Sift4G

Pathogenic

0.0

D;D;D;.

Polyphen

1.0

D;D;.;.

Vest4

0.40

MVP

0.82

MPC

0.76

ClinPred

0.70

GERP RS

3.0

Varity_R

0.085

gMVP

0.60

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