10-101131896-A-G

Position:

chr10-101131896-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_005521.4(TLX1):c.355A>G(p.Ser119Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,395,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000097 ( 0 hom. )

Consequence

TLX1
NM_005521.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.79

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08600694).

BP6

Variant 10-101131896-A-G is Benign according to our data. Variant chr10-101131896-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2383636.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 79 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TLX1	NM_005521.4 linkuse as main transcript	c.355A>G	p.Ser119Gly	missense_variant	1/3	ENST00000370196.11	NP_005512.1
TLX1	NM_001195517.2 linkuse as main transcript	c.355A>G	p.Ser119Gly	missense_variant	1/3		NP_001182446.1
TLX1	XM_011539744.4 linkuse as main transcript	c.355A>G	p.Ser119Gly	missense_variant	1/3		XP_011538046.1
TLX1NB	NR_130724.1 linkuse as main transcript	n.580-4798T>C		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.355A>G	p.Ser119Gly	missense_variant	1/3	1	NM_005521.4	ENSP00000359215	P1	P31314-1
TLX1	ENST00000467928.2 linkuse as main transcript	c.355A>G	p.Ser119Gly	missense_variant	1/3	1		ENSP00000434914		P31314-2
TLX1	ENST00000463716.3 linkuse as main transcript	c.169A>G	p.Ser57Gly	missense_variant	1/2	3		ENSP00000434358

Frequencies

GnomAD3 genomes

AF:

0.000520

AC:

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00253

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000958

GnomAD4 exome

AF:

0.0000973

AC:

121

AN:

1243168

Hom.:

Cov.:

AF XY:

0.0000987

AC XY:

AN XY:

607722

show subpopulations

Gnomad4 AFR exome

AF:

0.00184

Gnomad4 AMR exome

AF:

0.000235

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00180

Gnomad4 SAS exome

AF:

0.0000358

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000887

Gnomad4 OTH exome

AF:

0.000214

GnomAD4 genome

AF:

0.000520

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.000646

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00253

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000948

Bravo

AF:

0.000631

Asia WGS

AF:

0.00203

AC:

AN:

3462

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.28

DEOGEN2

Benign

0.21

T;.;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.35

T;T;T

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.086

T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

-1.1

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.40

N;N;.

REVEL

Benign

0.25

Sift

Benign

0.39

T;T;.

Sift4G

Benign

0.21

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.13

MutPred

0.30

Loss of glycosylation at S119 (P = 0.0057);Loss of glycosylation at S119 (P = 0.0057);.;

MVP

0.72

ClinPred

0.035

GERP RS

3.0

Varity_R

0.077

gMVP

0.28

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