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GeneBe

6-133889667-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_003206.4(TCF21):c.270C>T(p.Ala90=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00872 in 1,613,866 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0075 ( 9 hom., cov: 32)
Exomes 𝑓: 0.0089 ( 99 hom. )

Consequence

TCF21
NM_003206.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.668
Variant links:
Genes affected
TCF21 (HGNC:11632): (transcription factor 21) TCF21 encodes a transcription factor of the basic helix-loop-helix family. The TCF21 product is mesoderm specific, and expressed in embryonic epicardium, mesenchyme-derived tissues of lung, gut, gonad, and both mesenchymal and glomerular epithelial cells in the kidney. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
TARID (HGNC:50506): (TCF21 antisense RNA inducing promoter demethylation)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-133889667-C-T is Benign according to our data. Variant chr6-133889667-C-T is described in ClinVar as [Benign]. Clinvar id is 769693.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.668 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00885 (12936/1461660) while in subpopulation SAS AF= 0.016 (1380/86254). AF 95% confidence interval is 0.0153. There are 99 homozygotes in gnomad4_exome. There are 6684 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1140 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TCF21NM_003206.4 linkuse as main transcriptc.270C>T p.Ala90= synonymous_variant 1/2 ENST00000367882.5
TCF21NM_198392.3 linkuse as main transcriptc.270C>T p.Ala90= synonymous_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TCF21ENST00000367882.5 linkuse as main transcriptc.270C>T p.Ala90= synonymous_variant 1/21 NM_003206.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00750
AC:
1140
AN:
152086
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00162
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00484
Gnomad ASJ
AF:
0.00923
Gnomad EAS
AF:
0.00740
Gnomad SAS
AF:
0.0176
Gnomad FIN
AF:
0.00669
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0111
Gnomad OTH
AF:
0.00956
GnomAD3 exomes
AF:
0.00878
AC:
2201
AN:
250802
Hom.:
19
AF XY:
0.00904
AC XY:
1228
AN XY:
135776
show subpopulations
Gnomad AFR exome
AF:
0.00161
Gnomad AMR exome
AF:
0.00347
Gnomad ASJ exome
AF:
0.0112
Gnomad EAS exome
AF:
0.00403
Gnomad SAS exome
AF:
0.0180
Gnomad FIN exome
AF:
0.00753
Gnomad NFE exome
AF:
0.00968
Gnomad OTH exome
AF:
0.00932
GnomAD4 exome
AF:
0.00885
AC:
12936
AN:
1461660
Hom.:
99
Cov.:
34
AF XY:
0.00919
AC XY:
6684
AN XY:
727150
show subpopulations
Gnomad4 AFR exome
AF:
0.000866
Gnomad4 AMR exome
AF:
0.00356
Gnomad4 ASJ exome
AF:
0.0111
Gnomad4 EAS exome
AF:
0.00353
Gnomad4 SAS exome
AF:
0.0160
Gnomad4 FIN exome
AF:
0.00730
Gnomad4 NFE exome
AF:
0.00883
Gnomad4 OTH exome
AF:
0.0112
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00752
AC:
1144
AN:
152206
Hom.:
9
Cov.:
32
AF XY:
0.00742
AC XY:
552
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.00161
Gnomad4 AMR
AF:
0.00483
Gnomad4 ASJ
AF:
0.00923
Gnomad4 EAS
AF:
0.00723
Gnomad4 SAS
AF:
0.0176
Gnomad4 FIN
AF:
0.00669
Gnomad4 NFE
AF:
0.0111
Gnomad4 OTH
AF:
0.0118
Alfa
AF:
0.00933
Hom.:
5
Bravo
AF:
0.00615
Asia WGS
AF:
0.0400
AC:
139
AN:
3478
EpiCase
AF:
0.00976
EpiControl
AF:
0.00960

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 submitterclinical testingInvitaeJul 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
Cadd
Benign
13
Dann
Benign
0.95

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

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

Other links and lift over

dbSNP: rs3777890; hg19: chr6-134210805; API