1-47225578-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001290403.2(TAL1):c.311C>T(p.Ala104Val) variant causes a missense change. The variant allele was found at a frequency of 0.000276 in 1,284,062 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A104S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

TAL1
NM_001290403.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.91

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0095130205).

BP6

Variant 1-47225578-G-A is Benign according to our data. Variant chr1-47225578-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038868.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 213 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAL1	NM_001290403.2 linkuse as main transcript	c.311C>T	p.Ala104Val	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.311C>T	p.Ala104Val	missense_variant	3/5		NM_001290403.2	P1	P17542-1
TAL1	ENST00000294339.3 linkuse as main transcript	c.311C>T	p.Ala104Val	missense_variant	2/4	1		P1	P17542-1
TAL1	ENST00000371884.6 linkuse as main transcript	c.311C>T	p.Ala104Val	missense_variant	3/5	1		P1	P17542-1

Frequencies

GnomAD3 genomes

AF:

0.00140

AC:

213

AN:

151938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00497

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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:

0.000125

AC:

141

AN:

1132016

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

543240

show subpopulations

Gnomad4 AFR exome

AF:

0.00531

Gnomad4 AMR exome

AF:

0.000232

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000324

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000209

Gnomad4 OTH exome

AF:

0.000305

GnomAD4 genome

AF:

0.00140

AC:

213

AN:

152046

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

103

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00496

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.00153

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TAL1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 26, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.073

T;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.90

M_CAP

Pathogenic

0.92

MetaRNN

Benign

0.0095

T;T

MetaSVM

Uncertain

-0.055

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.52

N;N

REVEL

Uncertain

0.32

Sift

Benign

0.10

T;T

Sift4G

Benign

0.60

T;T

Polyphen

0.0010

B;B

Vest4

0.16

MutPred

0.14

Loss of glycosylation at P105 (P = 0.0617);Loss of glycosylation at P105 (P = 0.0617);

MVP

0.69

MPC

0.67

ClinPred

0.46

GERP RS

0.99

Varity_R

0.055

gMVP

0.29

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