9-105662767-A-T

Variant names:

• chr9-105662767-A-T
• rs766613487
• NM_005421.3:c.271A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005421.3(TAL2):​c.271A>T​(p.Thr91Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T91A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TAL2 NM_005421.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44
• Publications: 0 publications found

Genes affected

TAL2 (HGNC:11557): (TAL bHLH transcription factor 2) This intronless gene encodes a helix-loop-helix protein. Translocations between this gene on chromosome 9 and the T-cell receptor beta-chain locus on chromosome 7 have been associated with activation of the T-cell acute lymphocytic leukemia 2 gene and T-cell acute lymphoblastic leukemia. [provided by RefSeq, Mar 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1401872).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005421.3. 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
	TAL2	NM_005421.3	MANE Select	c.271A>T	p.Thr91Ser	missense	Exon 1 of 1	NP_005412.1	Q16559

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAL2	ENST00000334077.6	TSL:6 MANE Select	c.271A>T	p.Thr91Ser	missense	Exon 1 of 1	ENSP00000334547.3	Q16559

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396666 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 688602

African (AFR) AF: 0.00 AC: 0 AN: 31162

American (AMR) AF: 0.00 AC: 0 AN: 35070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22068

East Asian (EAS) AF: 0.00 AC: 0 AN: 38634

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 73952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5458

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081398

Other (OTH) AF: 0.00 AC: 0 AN: 57572

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.24	T
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.14	T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	0.55	N
PhyloP100		3.4
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.27
Sift	Benign	0.074	T
Sift4G	Benign	0.56	T
Polyphen		0.017	B
Vest4		0.11
MutPred		0.26		Gain of disorder (P = 0.0334)
MVP		0.73
MPC		0.026
ClinPred		0.55	D
GERP RS		4.4
PromoterAI		0.024	Neutral
Varity_R		0.074
gMVP		0.31
Mutation Taster		=64/36	polymorphism

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: rs766613487; hg19: chr9-108425048;