rs2742038

Variant names:

• chr10-101137330-C-T
• rs2742038
• NM_005521.4:c.*417C>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.*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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 9 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=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLX1	NM_005521.4	MANE Select	c.*417C>T		3_prime_UTR	Exon 3 of 3	NP_005512.1	P31314-1
	TLX1	NM_001195517.2		c.*659C>T		3_prime_UTR	Exon 3 of 3	NP_001182446.1	P31314-2
	TLX1NB	NR_130724.1		n.579+3358G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLX1	ENST00000370196.11	TSL:1 MANE Select	c.*417C>T		3_prime_UTR	Exon 3 of 3	ENSP00000359215.6	P31314-1
	TLX1	ENST00000467928.2	TSL:1	c.*659C>T		3_prime_UTR	Exon 3 of 3	ENSP00000434914.2	P31314-2
	TLX1NB	ENST00000747503.1		n.731+3358G>A		intron	N/A

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

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

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

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: 57 AN: 292

European-Non Finnish (NFE) AF: 0.143 AC: 9737 AN: 68010

Other (OTH) AF: 0.177 AC: 374 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		0.15
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: rs2742038; hg19: chr10-102897087;