dbSNP rs2742038: TLX1:c.*417C>T (chr10-101137330-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005521.4(TLX1):c.*417C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 297,858 control chromosomes in the GnomAD database, including 4,353 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2193 hom., cov: 33)

Exomes 𝑓: 0.17 ( 2160 hom. )

Consequence

TLX1
NM_005521.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.148

Publications

9 publications found

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:

ENSG00000297403 (HGNC:):

ENSG00000297403 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
TLX1	NM_005521.4 link	c.*417C>T	3_prime_UTR_variant	Exon 3 of 3	ENST00000370196.11	NP_005512.1
TLX1	NM_001195517.2 link	c.*659C>T	3_prime_UTR_variant	Exon 3 of 3		NP_001182446.1
TLX1	XM_011539744.4 link	c.*417C>T	3_prime_UTR_variant	Exon 3 of 3		XP_011538046.1
TLX1NB	NR_130724.1 link	n.579+3358G>A	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLX1	ENST00000370196.11 link	c.*417C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_005521.4	ENSP00000359215.6

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25117

AN:

152100

Hom.:

2193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.282

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.175

GnomAD4 exome

AF:

0.166

AC:

24219

AN:

145640

Hom.:

2160

Cov.:

AF XY:

0.171

AC XY:

12089

AN XY:

70540

show subpopulations

African (AFR)

AF:

0.165

AC:

968

AN:

5872

American (AMR)

AF:

0.205

AC:

1290

AN:

6292

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

965

AN:

6584

East Asian (EAS)

AF:

0.241

AC:

3542

AN:

14722

South Asian (SAS)

AF:

0.282

AC:

2450

AN:

8688

European-Finnish (FIN)

AF:

0.115

AC:

329

AN:

2860

Middle Eastern (MID)

AF:

0.194

AC:

140

AN:

720

European-Non Finnish (NFE)

AF:

0.143

AC:

12863

AN:

89738

Other (OTH)

AF:

0.165

AC:

1672

AN:

10164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1050

2101

3151

4202

5252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.165

AC:

25120

AN:

152218

Hom.:

2193

Cov.:

AF XY:

0.167

AC XY:

12408

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.174

AC:

7239

AN:

41514

American (AMR)

AF:

0.191

AC:

2929

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

519

AN:

3468

East Asian (EAS)

AF:

0.281

AC:

1456

AN:

5178

South Asian (SAS)

AF:

0.289

AC:

1393

AN:

4824

European-Finnish (FIN)

AF:

0.113

AC:

1203

AN:

10610

Middle Eastern (MID)

AF:

0.195

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.143

AC:

9737

AN:

68010

Other (OTH)

AF:

0.177

AC:

374

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1084

2168

3253

4337

5421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.157

Hom.:

2867

Bravo

AF:

0.170

Asia WGS

AF:

0.313

AC:

1090

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over