chr22-42171084-T-C

Variant names:

• chr22-42171084-T-C
• rs9306356
• NM_001378418.1:c.5750-1188A>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.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
• Publications: 3 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=-0.74).
• 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 rank	MANE	Protein	UniProt
TCF20	NM_001378418.1	c.5750-1188A>G		intron_variant	Intron 3 of 5	ENST00000677622.1	NP_001365347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF20	ENST00000677622.1	c.5750-1188A>G		intron_variant	Intron 3 of 5		NM_001378418.1	ENSP00000503828.1

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

African (AFR) AF: 0.118 AC: 4916 AN: 41528

American (AMR) AF: 0.0698 AC: 1068 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3472

East Asian (EAS) AF: 0.0283 AC: 147 AN: 5194

South Asian (SAS) AF: 0.109 AC: 527 AN: 4824

European-Finnish (FIN) AF: 0.0235 AC: 249 AN: 10618

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0838 AC: 5702 AN: 68010

Other (OTH) AF: 0.0931 AC: 197 AN: 2116

Alfa AF: 0.0837 Hom.: 1317

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
PhyloP100		-0.18
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: rs9306356; hg19: chr22-42567090;