rs5758651

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2671 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29627 hom. )

Consequence

TCF20
NM_001378418.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00700

Publications

39 publications found

Variant links:

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

TCF20 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TCF20	NM_001378418.1 link	c.2164A>G	p.Ser722Gly	missense_variant	Exon 2 of 6	ENST00000677622.1	NP_001365347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF20	ENST00000677622.1 link	c.2164A>G	p.Ser722Gly	missense_variant	Exon 2 of 6		NM_001378418.1	ENSP00000503828.1		Q9UGU0-1

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27179

AN:

152044

Hom.:

2671

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.182

AC:

45801

AN:

251444

AF XY:

0.181

show subpopulations

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 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.:

AF XY:

0.194

AC XY:

141393

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.135

AC:

4535

AN:

33480

American (AMR)

AF:

0.124

AC:

5567

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

6752

AN:

26134

East Asian (EAS)

AF:

0.309

AC:

12284

AN:

39698

South Asian (SAS)

AF:

0.134

AC:

11588

AN:

86258

European-Finnish (FIN)

AF:

0.105

AC:

5632

AN:

53414

Middle Eastern (MID)

AF:

0.142

AC:

817

AN:

5768

European-Non Finnish (NFE)

AF:

0.205

AC:

227860

AN:

1112006

Other (OTH)

AF:

0.190

AC:

11497

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

17249

34499

51748

68998

86247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7906

15812

23718

31624

39530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.179

AC:

27168

AN:

152162

Hom.:

2671

Cov.:

AF XY:

0.172

AC XY:

12817

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.137

AC:

5682

AN:

41508

American (AMR)

AF:

0.149

AC:

2278

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

899

AN:

3472

East Asian (EAS)

AF:

0.337

AC:

1743

AN:

5168

South Asian (SAS)

AF:

0.144

AC:

692

AN:

4816

European-Finnish (FIN)

AF:

0.0996

AC:

1056

AN:

10600

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.208

AC:

14162

AN:

67988

Other (OTH)

AF:

0.164

AC:

346

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1125

2250

3375

4500

5625

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.200

Hom.:

9398

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 23, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.7

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.043

T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.55

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.90

N;N

PhyloP100

0.0070

PrimateAI

Benign

0.44

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

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.22

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over