rs1051723

Variant names:

• chr10-101137300-C-T
• rs1051723
• NM_005521.4:c.*387C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415
• Publications: 5 publications found

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]

TLX1NB (HGNC:37183): (TLX1 neighbor)

ENSG00000297403 (HGNC:):

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLX1	NM_005521.4	c.*387C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000370196.11	NP_005512.1
TLX1	NM_001195517.2	c.*629C>T		3_prime_UTR_variant	Exon 3 of 3		NP_001182446.1
TLX1	XM_011539744.4	c.*387C>T		3_prime_UTR_variant	Exon 3 of 3		XP_011538046.1
TLX1NB	NR_130724.1	n.579+3388G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLX1	ENST00000370196.11	c.*387C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_005521.4	ENSP00000359215.6

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33354 AN: 152098 Hom.: 4406 Cov.: 33

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.: 0 AF XY: 0.241 AC XY: 19971 AN XY: 82972

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

GnomAD4 genome AF: 0.219 AC: 33367 AN: 152216 Hom.: 4409 Cov.: 33 AF XY: 0.217 AC XY: 16154 AN XY: 74418

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: 54 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20446 AN: 67994

Other (OTH) AF: 0.222 AC: 469 AN: 2110

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1051723; hg19: chr10-102897057;