Genetic Variant NM_001290403.2:c.821G>A (chr1-47219895-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001290403.2(TAL1):c.821G>A(p.Gly274Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000070 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TAL1
NM_001290403.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12771049).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290403.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAL1	NM_001290403.2	MANE Select	c.821G>A	p.Gly274Asp	missense	Exon 5 of 5	NP_001277332.1	P17542-1
TAL1	NM_001287347.2		c.821G>A	p.Gly274Asp	missense	Exon 5 of 5	NP_001274276.1	Q16509
TAL1	NM_001290404.1		c.821G>A	p.Gly274Asp	missense	Exon 6 of 6	NP_001277333.1	P17542-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAL1	ENST00000691006.1	MANE Select	c.821G>A	p.Gly274Asp	missense	Exon 5 of 5	ENSP00000510655.1	P17542-1
TAL1	ENST00000294339.3	TSL:1	c.821G>A	p.Gly274Asp	missense	Exon 4 of 4	ENSP00000294339.3	P17542-1
TAL1	ENST00000371884.6	TSL:1	c.821G>A	p.Gly274Asp	missense	Exon 5 of 5	ENSP00000360951.1	P17542-1

Frequencies

GnomAD3 genomes

AF:

0.0000698

AC:

AN:

143230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD2 exomes

AF:

0.0000263

AC:

AN:

190358

AF XY:

0.00000963

show subpopulations

Gnomad AFR exome

AF:

0.000241

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000596

Gnomad NFE exome

AF:

0.0000119

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000271

AC:

AN:

405182

Hom.:

Cov.:

AF XY:

0.0000182

AC XY:

AN XY:

219442

show subpopulations

African (AFR)

AF:

0.000353

AC:

AN:

11344

American (AMR)

AF:

0.00

AC:

AN:

32046

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9282

East Asian (EAS)

AF:

0.00

AC:

AN:

14180

South Asian (SAS)

AF:

0.00

AC:

AN:

59454

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28786

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1200

European-Non Finnish (NFE)

AF:

0.0000259

AC:

AN:

231540

Other (OTH)

AF:

0.0000576

AC:

AN:

17350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000698

AC:

AN:

143230

Hom.:

Cov.:

AF XY:

0.0000719

AC XY:

AN XY:

69574

show subpopulations

African (AFR)

AF:

0.000250

AC:

AN:

39974

American (AMR)

AF:

0.00

AC:

AN:

14554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3310

East Asian (EAS)

AF:

0.00

AC:

AN:

4178

South Asian (SAS)

AF:

0.00

AC:

AN:

3888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64912

Other (OTH)

AF:

0.00

AC:

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.00000859

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.63

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.44

MutationAssessor

Benign

1.6

PhyloP100

1.6

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.3

REVEL

Benign

0.19

Sift

Uncertain

0.0070

Sift4G

Benign

0.075

Polyphen

0.097

Vest4

0.25

MVP

0.74

MPC

0.90

ClinPred

0.080

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.27

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over