NM_003200.5:c.72+42T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003200.5(TCF3):c.72+42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,515,796 control chromosomes in the GnomAD database, including 183,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 27521 hom., cov: 32)

Exomes 𝑓: 0.46 ( 155861 hom. )

Consequence

TCF3
NM_003200.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.25

Publications

20 publications found

Variant links:

Genes affected

TCF3 (HGNC:11633): (transcription factor 3) This gene encodes a member of the E protein (class I) family of helix-loop-helix transcription factors. E proteins activate transcription by binding to regulatory E-box sequences on target genes as heterodimers or homodimers, and are inhibited by heterodimerization with inhibitor of DNA-binding (class IV) helix-loop-helix proteins. E proteins play a critical role in lymphopoiesis, and the encoded protein is required for B and T lymphocyte development. Deletion of this gene or diminished activity of the encoded protein may play a role in lymphoid malignancies. This gene is also involved in several chromosomal translocations that are associated with lymphoid malignancies including pre-B-cell acute lymphoblastic leukemia (t(1;19), with PBX1), childhood leukemia (t(19;19), with TFPT) and acute leukemia (t(12;19), with ZNF384). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, Sep 2011]

TCF3 Gene-Disease associations (from GenCC):

autosomal agammaglobulinemia
Inheritance: AD, SD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
agammaglobulinemia 8, autosomal dominant
Inheritance: AD, AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
agammaglobulinemia 8b, autosomal recessive
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

TCF3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 19-1650135-A-G is Benign according to our data. Variant chr19-1650135-A-G is described in ClinVar as Benign. ClinVar VariationId is 1185424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003200.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TCF3	NM_003200.5	MANE Select	c.72+42T>C	intron	N/A	NP_003191.1	P15923-1
TCF3	NM_001136139.4	MANE Plus Clinical	c.72+42T>C	intron	N/A	NP_001129611.1	P15923-2
TCF3	NM_001351778.2		c.72+42T>C	intron	N/A	NP_001338707.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TCF3	ENST00000262965.12	TSL:1 MANE Select	c.72+42T>C	intron	N/A	ENSP00000262965.5	P15923-1
TCF3	ENST00000588136.7	TSL:2 MANE Plus Clinical	c.72+42T>C	intron	N/A	ENSP00000468487.1	P15923-2
TCF3	ENST00000931972.1		c.72+42T>C	intron	N/A	ENSP00000602031.1

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86587

AN:

151790

Hom.:

27479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.829

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.582

Gnomad ASJ

AF:

0.405

Gnomad EAS

AF:

0.890

Gnomad SAS

AF:

0.718

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.532

GnomAD2 exomes

AF:

0.541

AC:

81014

AN:

149844

AF XY:

0.543

show subpopulations

Gnomad AFR exome

AF:

0.839

Gnomad AMR exome

AF:

0.631

Gnomad ASJ exome

AF:

0.397

Gnomad EAS exome

AF:

0.869

Gnomad FIN exome

AF:

0.337

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.484

GnomAD4 exome

AF:

0.461

AC:

628144

AN:

1363888

Hom.:

155861

Cov.:

AF XY:

0.466

AC XY:

314227

AN XY:

674408

show subpopulations

African (AFR)

AF:

0.845

AC:

26423

AN:

31266

American (AMR)

AF:

0.627

AC:

22255

AN:

35478

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

10130

AN:

24918

East Asian (EAS)

AF:

0.903

AC:

32629

AN:

36128

South Asian (SAS)

AF:

0.700

AC:

54960

AN:

78548

European-Finnish (FIN)

AF:

0.378

AC:

16057

AN:

42500

Middle Eastern (MID)

AF:

0.455

AC:

2542

AN:

5590

European-Non Finnish (NFE)

AF:

0.413

AC:

435034

AN:

1052554

Other (OTH)

AF:

0.494

AC:

28114

AN:

56906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

13471

26942

40414

53885

67356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13804

27608

41412

55216

69020

<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:

0.571

AC:

86686

AN:

151908

Hom.:

27521

Cov.:

AF XY:

0.576

AC XY:

42813

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.830

AC:

34370

AN:

41430

American (AMR)

AF:

0.582

AC:

8891

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

1403

AN:

3468

East Asian (EAS)

AF:

0.889

AC:

4586

AN:

5156

South Asian (SAS)

AF:

0.716

AC:

3449

AN:

4818

European-Finnish (FIN)

AF:

0.418

AC:

4397

AN:

10522

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.413

AC:

28072

AN:

67932

Other (OTH)

AF:

0.530

AC:

1120

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1557

3113

4670

6226

7783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

718

1436

2154

2872

3590

<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:

0.473

Hom.:

57655

Bravo

AF:

0.593

Asia WGS

AF:

0.785

AC:

2727

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Agammaglobulinemia 8, autosomal dominant (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.3

(source)

DANN

Benign

0.62

PhyloP100

-1.3

PromoterAI

0.0064

Neutral

(source)

Mutation Taster

=19/81

disease causing

(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