Variant 1-47219866-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001290403.2(TAL1):c.850G>A(p.Val284Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000044 in 1,592,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

TAL1
NM_001290403.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.72

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:

TAL1 (HGNC:):

TAL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06404528).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAL1	NM_001290403.2 linkuse as main transcript	c.850G>A	p.Val284Met	missense_variant	5/5	ENST00000691006.1	NP_001277332.1	P17542-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TAL1	ENST00000691006.1 linkuse as main transcript	c.850G>A	p.Val284Met	missense_variant	5/5		NM_001290403.2	ENSP00000510655.1	P17542-1
TAL1	ENST00000294339.3 linkuse as main transcript	c.850G>A	p.Val284Met	missense_variant	4/4	1		ENSP00000294339.3	P17542-1
TAL1	ENST00000371884.6 linkuse as main transcript	c.850G>A	p.Val284Met	missense_variant	5/5	1		ENSP00000360951.1	P17542-1
TAL1	ENST00000459729.1 linkuse as main transcript	n.618G>A		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000347

AC:

AN:

1439986

Hom.:

Cov.:

AF XY:

0.00000421

AC XY:

AN XY:

713072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000229

Gnomad4 ASJ exome

AF:

0.0000402

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Nov 11, 2024

The c.850G>A (p.V284M) alteration is located in exon 4 (coding exon 3) of the TAL1 gene. This alteration results from a G to A substitution at nucleotide position 850, causing the valine (V) at amino acid position 284 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

Benign

0.16

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.055

T;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.81

.;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.064

T;T

MetaSVM

Uncertain

-0.040

MutationAssessor

Benign

-0.41

N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.64

N;N

REVEL

Benign

0.25

Sift

Benign

0.99

T;T

Sift4G

Benign

0.36

T;T

Polyphen

0.29

B;B

Vest4

0.064

MutPred

0.18

Loss of glycosylation at S289 (P = 0.2125);Loss of glycosylation at S289 (P = 0.2125);

MVP

0.44

MPC

0.70

ClinPred

0.72

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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