rs1052918

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-1609670-T-A
• chr19-1609670-T-C
• chr19-1609670-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003200.5(TCF3):​c.*2037A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000671 in 149,114 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000067 (0 hom., cov: 30)
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF3	NM_003200.5	c.*2037A>T		3_prime_UTR_variant	Exon 19 of 19	ENST00000262965.12	NP_003191.1
TCF3	NM_001136139.4	c.*1703A>T		3_prime_UTR_variant	Exon 20 of 20	ENST00000588136.7	NP_001129611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF3	ENST00000262965.12	c.*2037A>T		3_prime_UTR_variant	Exon 19 of 19	1	NM_003200.5	ENSP00000262965.5
TCF3	ENST00000588136.7	c.*1703A>T		3_prime_UTR_variant	Exon 20 of 20	2	NM_001136139.4	ENSP00000468487.1

Frequencies

GnomAD3 genomes AF: 0.00000671 AC: 1 AN: 149114 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000247

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

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00000671 AC: 1 AN: 149114 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 1 AN XY: 72718

African (AFR) AF: 0.0000247 AC: 1 AN: 40494

American (AMR) AF: 0.00 AC: 0 AN: 15056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3418

East Asian (EAS) AF: 0.00 AC: 0 AN: 5018

South Asian (SAS) AF: 0.00 AC: 0 AN: 4614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66842

Other (OTH) AF: 0.00 AC: 0 AN: 2024

Alfa AF: 0.00 Hom.: 4002

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.62
PhyloP100		-0.70

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;