Genetic Variant TAL1:p.Pro132Arg (chr1-47225494-G-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001290403.2(TAL1):c.395C>G(p.Pro132Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000131 in 1,235,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

TAL1
NM_001290403.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.41808328).

BS2

High AC in GnomAd4 at 20 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.395C>G	p.Pro132Arg	missense	Exon 3 of 5	NP_001277332.1	P17542-1
TAL1	NM_001287347.2		c.395C>G	p.Pro132Arg	missense	Exon 3 of 5	NP_001274276.1	Q16509
TAL1	NM_001290404.1		c.395C>G	p.Pro132Arg	missense	Exon 4 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.395C>G	p.Pro132Arg	missense	Exon 3 of 5	ENSP00000510655.1	P17542-1
TAL1	ENST00000294339.3	TSL:1	c.395C>G	p.Pro132Arg	missense	Exon 2 of 4	ENSP00000294339.3	P17542-1
TAL1	ENST00000371884.6	TSL:1	c.395C>G	p.Pro132Arg	missense	Exon 3 of 5	ENSP00000360951.1	P17542-1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00

AC:

AN:

314

AF XY:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000131

AC:

142

AN:

1083248

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

512210

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22852

American (AMR)

AF:

0.000120

AC:

AN:

8344

Ashkenazi Jewish (ASJ)

AF:

0.000699

AC:

AN:

14314

East Asian (EAS)

AF:

0.00

AC:

AN:

26464

South Asian (SAS)

AF:

0.000705

AC:

AN:

19868

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21224

Middle Eastern (MID)

AF:

0.00103

AC:

AN:

2924

European-Non Finnish (NFE)

AF:

0.000108

AC:

100

AN:

923480

Other (OTH)

AF:

0.000320

AC:

AN:

43778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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

AF:

0.000131

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41558

American (AMR)

AF:

0.000131

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

67968

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.000140

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

0.23

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.91

MetaRNN

Benign

0.42

MetaSVM

Pathogenic

0.97

MutationAssessor

Benign

1.6

PhyloP100

3.6

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.41

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

0.92

Vest4

0.20

MutPred

0.32

Loss of glycosylation at P132 (P = 0.0095)

MVP

0.70

MPC

1.1

ClinPred

0.97

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.45

gMVP

0.65

Mutation Taster

=85/15

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

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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