dbSNP rs369095303: TLX1:p.Pro158Arg (chr10-101132014-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005521.4(TLX1):c.473C>G(p.Pro158Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000117 in 1,372,182 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P158L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TLX1
NM_005521.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.88

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:37183): (TLX1 neighbor)

TLX1NB links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLX1	NM_005521.4 link	c.473C>G	p.Pro158Arg	missense_variant	Exon 1 of 3	ENST00000370196.11	NP_005512.1	P31314-1
TLX1	NM_001195517.2 link	c.473C>G	p.Pro158Arg	missense_variant	Exon 1 of 3		NP_001182446.1	P31314-2
TLX1	XM_011539744.4 link	c.473C>G	p.Pro158Arg	missense_variant	Exon 1 of 3		XP_011538046.1
TLX1NB	NR_130724.1 link	n.580-4916G>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLX1	ENST00000370196.11 link	c.473C>G	p.Pro158Arg	missense_variant	Exon 1 of 3	1	NM_005521.4	ENSP00000359215.6		P31314-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000573

AC:

AN:

174446

AF XY:

0.0000101

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000118

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1372182

Hom.:

Cov.:

AF XY:

0.0000103

AC XY:

AN XY:

681736

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28586

American (AMR)

AF:

0.00

AC:

AN:

35070

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23860

East Asian (EAS)

AF:

0.00

AC:

AN:

32352

South Asian (SAS)

AF:

0.00

AC:

AN:

76926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5534

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

1076776

Other (OTH)

AF:

0.00

AC:

AN:

56744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000842

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

D;.;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.76

T;T;T

M_CAP

Pathogenic

0.75

MetaRNN

Uncertain

0.64

D;D;D

MetaSVM

Uncertain

0.56

MutationAssessor

Uncertain

2.0

M;M;.

PhyloP100

6.9

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-2.1

N;N;N

REVEL

Uncertain

0.51

Sift

Uncertain

0.0050

D;D;D

Sift4G

Benign

0.065

T;T;D

Polyphen

1.0

D;.;.

Vest4

0.55

MutPred

0.37

Loss of glycosylation at T156 (P = 0.08);Loss of glycosylation at T156 (P = 0.08);.;

MVP

0.96

ClinPred

0.88

GERP RS

3.5

PromoterAI

-0.048

Neutral

(source)

Varity_R

0.34

gMVP

0.63

Mutation Taster

=66/34

polymorphism

(source)

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

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rs369095303

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over