rs1051723

Positions:

• chr10-101137300-C-T

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TLX1	NM_005521.4	c.*387C>T		3_prime_UTR_variant	3/3	ENST00000370196.11	NP_005512.1
TLX1	NM_001195517.2	c.*629C>T		3_prime_UTR_variant	3/3		NP_001182446.1
TLX1	XM_011539744.4	c.*387C>T		3_prime_UTR_variant	3/3		XP_011538046.1
TLX1NB	NR_130724.1	n.579+3388G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLX1	ENST00000370196.11	c.*387C>T		3_prime_UTR_variant	3/3	1	NM_005521.4	ENSP00000359215.6
TLX1	ENST00000467928.2	c.*629C>T		3_prime_UTR_variant	3/3	1		ENSP00000434914.2

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

Gnomad4 AFR exome AF: 0.0722

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.247

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

Gnomad4 AFR AF: 0.0778

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.222

Alfa AF: 0.276 Hom.: 8232

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

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

Other links and lift over

dbSNP: rs1051723; hg19: chr10-102897057;