rs9306356

chr22-42171084-T-C

Variant summary

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

The NM_001378418.1(TCF20):c.5750-1188A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0887 in 152,270 control chromosomes in the GnomAD database, including 677 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 0.089 (677 hom., cov: 32)
• Consequence: TCF20 NM_001378418.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF20	NM_001378418.1	c.5750-1188A>G		intron_variant		ENST00000677622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF20	ENST00000677622.1	c.5750-1188A>G		intron_variant			NM_001378418.1	P2

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13489 AN: 152152 Hom.: 677 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0699

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0286

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0838

Gnomad OTH AF: 0.0946

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

GnomAD4 genome AF: 0.0887 AC: 13499 AN: 152270 Hom.: 677 Cov.: 32 AF XY: 0.0854 AC XY: 6363 AN XY: 74466

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0698

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0283

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0235

Gnomad4 NFE AF: 0.0838

Gnomad4 OTH AF: 0.0931

Alfa AF: 0.0772 Hom.: 392

Bravo AF: 0.0927

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	4.8
Dann	Benign	0.86

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

LitVar

Other links and lift over

dbSNP: rs9306356; hg19: chr22-42567090;