rs5751247

Variant names:

• chr22-42237048-T-C
• rs5751247
• NM_001378418.1:c.-36-21707A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-42237048-T-C
• chr22-42237048-T-G

Variant summary

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

The NM_001378418.1(TCF20):​c.-36-21707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 150,242 control chromosomes in the GnomAD database, including 5,777 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 0.27 (5777 hom., cov: 31)
• Consequence: TCF20 NM_001378418.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 12 publications found

Genes affected

TCF20 (HGNC:11631): (transcription factor 20) This gene encodes a transcription factor that recognizes the platelet-derived growth factor-responsive element in the matrix metalloproteinase 3 promoter. The encoded protein is thought to be a transcriptional coactivator, enhancing the activity of transcription factors such as JUN and SP1. Mutations in this gene are associated with autism spectrum disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

TCF20 Gene-Disease associations (from GenCC):

• developmental delay with variable intellectual impairment and behavioral abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Illumina
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF20	NM_001378418.1	c.-36-21707A>G		intron_variant	Intron 1 of 5	ENST00000677622.1	NP_001365347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF20	ENST00000677622.1	c.-36-21707A>G		intron_variant	Intron 1 of 5		NM_001378418.1	ENSP00000503828.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 40976 AN: 150128 Hom.: 5780 Cov.: 31

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.273 AC: 40968 AN: 150242 Hom.: 5777 Cov.: 31 AF XY: 0.263 AC XY: 19286 AN XY: 73460

African (AFR) AF: 0.285 AC: 11331 AN: 39774

American (AMR) AF: 0.211 AC: 3210 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1458 AN: 3466

East Asian (EAS) AF: 0.370 AC: 1910 AN: 5162

South Asian (SAS) AF: 0.256 AC: 1232 AN: 4810

European-Finnish (FIN) AF: 0.122 AC: 1294 AN: 10590

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19592 AN: 67948

Other (OTH) AF: 0.252 AC: 530 AN: 2104

Alfa AF: 0.280 Hom.: 8982

Bravo AF: 0.277

Asia WGS AF: 0.287 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.8
DANN	Benign	0.78
PhyloP100		0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5751247; hg19: chr22-42633054;