Variant 22-42168712-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001378418.1(TCF20):c.5824C>T(p.Pro1942Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000372 in 1,611,378 control chromosomes in the GnomAD database, including 4 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 (★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00023 ( 2 hom. )

Consequence

TCF20
NM_001378418.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.00

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005161375).

BP6

Variant 22-42168712-G-A is Benign according to our data. Variant chr22-42168712-G-A is described in ClinVar as [Benign]. Clinvar id is 2050454.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00171 (261/152280) while in subpopulation AFR AF= 0.00597 (248/41546). AF 95% confidence interval is 0.00536. There are 2 homozygotes in gnomad4. There are 125 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 261 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF20	NM_001378418.1 link	c.5824C>T	p.Pro1942Ser	missense_variant	5/6	ENST00000677622.1	NP_001365347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF20	ENST00000677622.1 link	c.5824C>T	p.Pro1942Ser	missense_variant	5/6		NM_001378418.1	ENSP00000503828.1		Q9UGU0-1

Frequencies

GnomAD3 genomes

AF:

0.00172

AC:

261

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00599

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000515

AC:

126

AN:

244782

Hom.:

AF XY:

0.000377

AC XY:

AN XY:

132636

show subpopulations

Gnomad AFR exome

AF:

0.00661

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.000265

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000722

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000232

AC:

339

AN:

1459098

Hom.:

Cov.:

AF XY:

0.000223

AC XY:

162

AN XY:

725702

show subpopulations

Gnomad4 AFR exome

AF:

0.00631

Gnomad4 AMR exome

AF:

0.000180

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000384

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000513

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.00171

AC:

261

AN:

152280

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00597

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000186

Hom.:

Bravo

AF:

0.00186

ESP6500AA

AF:

0.00772

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000651

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000179

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.035

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.65

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.1

PrimateAI

Benign

0.33

PROVEAN

Benign

0.43

REVEL

Benign

0.032

Sift

Benign

0.20

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.27

MVP

0.12

MPC

0.11

ClinPred

0.014

GERP RS

2.5

Varity_R

0.034

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over