Variant 10-101136821-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005521.4(TLX1):c.901T>C(p.Ser301Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,366 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

TLX1
NM_005521.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

TLX1 (HGNC:5056): (T cell leukemia homeobox 1) This gene encodes a nuclear transcription factor that belongs to the NK-linked or NK-like (NKL) subfamily of homeobox genes. The encoded protein is required for normal development of the spleen during embryogenesis. This protein is also involved in specification of neuronal cell fates. Ectopic expression of this gene due to chromosomal translocations is associated with certain T-cell acute lymphoblastic leukemias. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2010]

TLX1 links:

TLX1NB (HGNC:):

TLX1NB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TLX1	NM_005521.4 linkuse as main transcript	c.901T>C	p.Ser301Pro	missense_variant	3/3	ENST00000370196.11	NP_005512.1
TLX1	XM_011539744.4 linkuse as main transcript	c.937T>C	p.Ser313Pro	missense_variant	3/3		XP_011538046.1
TLX1	NM_001195517.2 linkuse as main transcript	c.*150T>C		3_prime_UTR_variant	3/3		NP_001182446.1
TLX1NB	NR_130724.1 linkuse as main transcript	n.579+3867A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLX1	ENST00000370196.11 linkuse as main transcript	c.901T>C	p.Ser301Pro	missense_variant	3/3	1	NM_005521.4	ENSP00000359215	P1	P31314-1
TLX1	ENST00000467928.2 linkuse as main transcript	c.*150T>C		3_prime_UTR_variant	3/3	1		ENSP00000434914		P31314-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461366

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726984

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:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 05, 2023

The c.901T>C (p.S301P) alteration is located in exon 3 (coding exon 3) of the TLX1 gene. This alteration results from a T to C substitution at nucleotide position 901, causing the serine (S) at amino acid position 301 to be replaced by a proline (P). 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

0.83

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.71

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.51

MetaRNN

Uncertain

0.71

MetaSVM

Uncertain

0.68

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

0.99

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.62

Sift

Uncertain

0.021

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.50

MutPred

0.40

Loss of catalytic residue at S301 (P = 0.0355);

MVP

0.95

ClinPred

0.98

GERP RS

4.4

Varity_R

0.73

gMVP

0.91

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