Variant 1-47225627-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001290403.2(TAL1):c.262G>A(p.Val88Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000677 in 1,383,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00070 ( 1 hom. )

Consequence

TAL1
NM_001290403.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

Variant links:

Genes affected

TAL1 (HGNC:11556): (TAL bHLH transcription factor 1, erythroid differentiation factor) Enables several functions, including DNA-binding transcription factor activity; E-box binding activity; and histone deacetylase binding activity. Involved in several processes, including myeloid cell differentiation; positive regulation of cellular component organization; and positive regulation of erythrocyte differentiation. Located in chromatin and nucleoplasm. Part of transcription regulator complex. Implicated in acute lymphoblastic leukemia. [provided by Alliance of Genome Resources, Apr 2022]

TAL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08200386).

BS2

High AC in GnomAd at 72 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAL1	NM_001290403.2 linkuse as main transcript	c.262G>A	p.Val88Met	missense_variant	3/5	ENST00000691006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAL1	ENST00000691006.1 linkuse as main transcript	c.262G>A	p.Val88Met	missense_variant	3/5		NM_001290403.2	P1	P17542-1
TAL1	ENST00000294339.3 linkuse as main transcript	c.262G>A	p.Val88Met	missense_variant	2/4	1		P1	P17542-1
TAL1	ENST00000371884.6 linkuse as main transcript	c.262G>A	p.Val88Met	missense_variant	3/5	1		P1	P17542-1

Frequencies

GnomAD3 genomes

AF:

0.000474

AC:

AN:

151882

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000751

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000666

AC:

AN:

19506

Hom.:

AF XY:

0.000925

AC XY:

AN XY:

11894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00353

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000866

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000702

AC:

864

AN:

1231040

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

421

AN XY:

601870

show subpopulations

Gnomad4 AFR exome

AF:

0.0000417

Gnomad4 AMR exome

AF:

0.000412

Gnomad4 ASJ exome

AF:

0.00295

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000999

Gnomad4 NFE exome

AF:

0.000763

Gnomad4 OTH exome

AF:

0.000613

GnomAD4 genome

AF:

0.000474

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000751

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000902

Hom.:

Bravo

AF:

0.000635

ExAC

AF:

0.000231

AC:

Asia WGS

AF:

0.000293

AC:

AN:

3424

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 04, 2022

The c.262G>A (p.V88M) alteration is located in exon 2 (coding exon 1) of the TAL1 gene. This alteration results from a G to A substitution at nucleotide position 262, causing the valine (V) at amino acid position 88 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

0.010

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.93

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.082

T;T

MetaSVM

Pathogenic

1.0

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.97

N;N

REVEL

Uncertain

0.58

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.94

P;P

Vest4

0.19

MVP

0.86

MPC

1.1

ClinPred

0.24

GERP RS

4.3

Varity_R

0.21

gMVP

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over