rs5758651

chr22-42213142-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378418.1(TCF20):c.2164A>G(p.Ser722Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,614,038 control chromosomes in the GnomAD database, including 32,298 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.18 (2671 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29627 hom.)
• Consequence: TCF20 NM_001378418.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00700

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032376945).
• BP6: Variant 22-42213142-T-C is Benign according to our data. Variant chr22-42213142-T-C is described in ClinVar as [Benign]. Clinvar id is 1302773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF20	NM_001378418.1	c.2164A>G	p.Ser722Gly	missense_variant	2/6	ENST00000677622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF20	ENST00000677622.1	c.2164A>G	p.Ser722Gly	missense_variant	2/6		NM_001378418.1	P2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27179 AN: 152044 Hom.: 2671 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0996

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.166

GnomAD3 exomes AF: 0.182 AC: 45801 AN: 251444 Hom.: 4802 AF XY: 0.181 AC XY: 24534 AN XY: 135906

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.363

Gnomad SAS exome AF: 0.134

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.200

Gnomad OTH exome AF: 0.183

GnomAD4 exome AF: 0.196 AC: 286532 AN: 1461876 Hom.: 29627 Cov.: 40 AF XY: 0.194 AC XY: 141393 AN XY: 727240

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.124

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.309

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.179 AC: 27168 AN: 152162 Hom.: 2671 Cov.: 32 AF XY: 0.172 AC XY: 12817 AN XY: 74378

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0996

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.164

Alfa AF: 0.203 Hom.: 7009

Bravo AF: 0.180

TwinsUK AF: 0.206 AC: 764

ALSPAC AF: 0.207 AC: 797

ESP6500AA AF: 0.132 AC: 582

ESP6500EA AF: 0.209 AC: 1797

ExAC AF: 0.181 AC: 22029

Asia WGS AF: 0.214 AC: 746 AN: 3478

EpiCase AF: 0.197

EpiControl AF: 0.199

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 23, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	8.7
Dann	Benign	0.87
DEOGEN2	Benign	0.043	T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.55	D
MetaRNN	Benign	0.0032	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.90	N;N
MutationTaster	Benign	0.39	P;P
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.11	N;N
REVEL	Benign	0.14
Sift	Benign	0.26	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.0	B;B
Vest4		0.045
MPC		0.10
ClinPred		0.0019	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.22

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: rs5758651; hg19: chr22-42609148; COSMIC: COSV59489310; COSMIC: COSV59489310;