dbSNP rs1051723: TLX1:c.*387C>T (chr10-101137300-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.*387C>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 0.234 in 320,940 control chromosomes in the GnomAD database, including 10,057 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 0.22 ( 4409 hom., cov: 33)

Exomes 𝑓: 0.25 ( 5648 hom. )

Consequence

TLX1
NM_005521.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.415

Publications

5 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=-0.69).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005521.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLX1	NM_005521.4	MANE Select	c.*387C>T	3_prime_UTR	Exon 3 of 3	NP_005512.1	P31314-1
TLX1	NM_001195517.2		c.*629C>T	3_prime_UTR	Exon 3 of 3	NP_001182446.1	P31314-2
TLX1NB	NR_130724.1		n.579+3388G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TLX1	ENST00000370196.11	TSL:1 MANE Select	c.*387C>T	3_prime_UTR	Exon 3 of 3	ENSP00000359215.6	P31314-1
TLX1	ENST00000467928.2	TSL:1	c.*629C>T	3_prime_UTR	Exon 3 of 3	ENSP00000434914.2	P31314-2
TLX1NB	ENST00000747503.1		n.731+3388G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33354

AN:

152098

Hom.:

4406

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0778

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.223

GnomAD4 exome

AF:

0.247

AC:

41635

AN:

168724

Hom.:

5648

Cov.:

AF XY:

0.241

AC XY:

19971

AN XY:

82972

show subpopulations

African (AFR)

AF:

0.0722

AC:

494

AN:

6840

American (AMR)

AF:

0.204

AC:

1356

AN:

6654

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

1641

AN:

7214

East Asian (EAS)

AF:

0.197

AC:

3044

AN:

15456

South Asian (SAS)

AF:

0.128

AC:

1638

AN:

12846

European-Finnish (FIN)

AF:

0.257

AC:

1074

AN:

4182

Middle Eastern (MID)

AF:

0.236

AC:

191

AN:

810

European-Non Finnish (NFE)

AF:

0.284

AC:

29396

AN:

103362

Other (OTH)

AF:

0.247

AC:

2801

AN:

11360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1575

3149

4724

6298

7873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

328

492

656

820

<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:

0.219

AC:

33367

AN:

152216

Hom.:

4409

Cov.:

AF XY:

0.217

AC XY:

16154

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0778

AC:

3232

AN:

41552

American (AMR)

AF:

0.225

AC:

3442

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

871

AN:

3472

East Asian (EAS)

AF:

0.166

AC:

861

AN:

5176

South Asian (SAS)

AF:

0.140

AC:

676

AN:

4826

European-Finnish (FIN)

AF:

0.288

AC:

3055

AN:

10592

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.301

AC:

20446

AN:

67994

Other (OTH)

AF:

0.222

AC:

469

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1295

2590

3886

5181

6476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.270

Hom.:

10040

Bravo

AF:

0.207

Asia WGS

AF:

0.138

AC:

481

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

0.41

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over