rs17478227

Positions:

• chr22-42258321-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378418.1(TCF20):​c.-37+12018G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,084 control chromosomes in the GnomAD database, including 1,634 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 0.13 (1634 hom., cov: 32)
• Consequence: TCF20 NM_001378418.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF20	NM_001378418.1	c.-37+12018G>C		intron_variant		ENST00000677622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF20	ENST00000677622.1	c.-37+12018G>C		intron_variant			NM_001378418.1	P2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19018 AN: 151966 Hom.: 1634 Cov.: 32

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.0994

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.0958

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.125 AC: 19012 AN: 152084 Hom.: 1634 Cov.: 32 AF XY: 0.118 AC XY: 8768 AN XY: 74352

Gnomad4 AFR AF: 0.0378

Gnomad4 AMR AF: 0.0993

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0867

Gnomad4 FIN AF: 0.0958

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.124

Alfa AF: 0.157 Hom.: 264

Bravo AF: 0.121

Asia WGS AF: 0.0540 AC: 191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.0
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17478227; hg19: chr22-42654327;