rs2742038

Positions:

• chr10-101137330-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000370196.11(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 ENST00000370196.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

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=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLX1	NM_005521.4	c.*417C>T		3_prime_UTR_variant	3/3	ENST00000370196.11	NP_005512.1
TLX1	NM_001195517.2	c.*659C>T		3_prime_UTR_variant	3/3		NP_001182446.1
TLX1	XM_011539744.4	c.*417C>T		3_prime_UTR_variant	3/3		XP_011538046.1
TLX1NB	NR_130724.1	n.579+3358G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLX1	ENST00000370196.11	c.*417C>T		3_prime_UTR_variant	3/3	1	NM_005521.4	ENSP00000359215	P1
TLX1	ENST00000467928.2	c.*659C>T		3_prime_UTR_variant	3/3	1		ENSP00000434914

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25117 AN: 152100 Hom.: 2193 Cov.: 33

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.: 0 AF XY: 0.171 AC XY: 12089 AN XY: 70540

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.241

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.165 AC: 25120 AN: 152218 Hom.: 2193 Cov.: 33 AF XY: 0.167 AC XY: 12408 AN XY: 74418

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.177

Alfa AF: 0.154 Hom.: 1921

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	11
DANN	Benign	0.85

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: rs2742038; hg19: chr10-102897087;