19-1609670-T-C

Variant names:

• chr19-1609670-T-C
• rs1052918
• NM_003200.5:c.*2037A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003200.5(TCF3):​c.*2037A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 222,518 control chromosomes in the GnomAD database, including 7,156 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (4687 hom., cov: 30)
  • Exomes 𝑓: 0.24 (2469 hom.)
• Consequence: TCF3 NM_003200.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703
• Publications: 11 publications found

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: SD, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• agammaglobulinemia 8, autosomal dominant

  Inheritance: AR, AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF3	NM_003200.5	MANE Select	c.*2037A>G		3_prime_UTR	Exon 19 of 19	NP_003191.1
	TCF3	NM_001136139.4	MANE Plus Clinical	c.*1703A>G		3_prime_UTR	Exon 20 of 20	NP_001129611.1
	TCF3	NM_001351779.2		c.*2037A>G		3_prime_UTR	Exon 19 of 19	NP_001338708.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF3	ENST00000262965.12	TSL:1 MANE Select	c.*2037A>G		3_prime_UTR	Exon 19 of 19	ENSP00000262965.5
	TCF3	ENST00000588136.7	TSL:2 MANE Plus Clinical	c.*1703A>G		3_prime_UTR	Exon 20 of 20	ENSP00000468487.1
	TCF3	ENST00000453954.6	TSL:5	c.*834A>G		3_prime_UTR	Exon 20 of 20	ENSP00000396363.3

Frequencies

GnomAD3 genomes AF: 0.247 AC: 36797 AN: 149048 Hom.: 4685 Cov.: 30

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.145

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.244 AC: 17888 AN: 73342 Hom.: 2469 Cov.: 0 AF XY: 0.243 AC XY: 8268 AN XY: 34004

African (AFR) AF: 0.281 AC: 953 AN: 3390

American (AMR) AF: 0.232 AC: 509 AN: 2196

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 1087 AN: 4606

East Asian (EAS) AF: 0.450 AC: 4712 AN: 10462

South Asian (SAS) AF: 0.167 AC: 105 AN: 630

European-Finnish (FIN) AF: 0.0926 AC: 5 AN: 54

Middle Eastern (MID) AF: 0.126 AC: 58 AN: 460

European-Non Finnish (NFE) AF: 0.199 AC: 9059 AN: 45442

Other (OTH) AF: 0.229 AC: 1400 AN: 6102

GnomAD4 genome AF: 0.247 AC: 36832 AN: 149176 Hom.: 4687 Cov.: 30 AF XY: 0.251 AC XY: 18253 AN XY: 72814

African (AFR) AF: 0.293 AC: 11909 AN: 40592

American (AMR) AF: 0.230 AC: 3470 AN: 15066

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 855 AN: 3418

East Asian (EAS) AF: 0.439 AC: 2195 AN: 5004

South Asian (SAS) AF: 0.174 AC: 801 AN: 4608

European-Finnish (FIN) AF: 0.287 AC: 2991 AN: 10434

Middle Eastern (MID) AF: 0.135 AC: 39 AN: 288

European-Non Finnish (NFE) AF: 0.209 AC: 13978 AN: 66820

Other (OTH) AF: 0.219 AC: 448 AN: 2042

Alfa AF: 0.200 Hom.: 4002

Bravo AF: 0.244

Asia WGS AF: 0.264 AC: 916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.54
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1052918; hg19: chr19-1609669;