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GeneBe

6-133889838-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003206.4(TCF21):c.441G>T(p.Pro147=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,612,738 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 6 hom. )

Consequence

TCF21
NM_003206.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.22
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 -11 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=-0.47).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-133889838-G-T is Benign according to our data. Variant chr6-133889838-G-T is described in ClinVar as [Benign]. Clinvar id is 731660.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=-1.22 with no splicing effect.
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 255 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TCF21NM_003206.4 linkuse as main transcriptc.441G>T p.Pro147= synonymous_variant 1/2 ENST00000367882.5
TCF21NM_198392.3 linkuse as main transcriptc.441G>T p.Pro147= synonymous_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TCF21ENST00000367882.5 linkuse as main transcriptc.441G>T p.Pro147= synonymous_variant 1/21 NM_003206.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00168
AC:
255
AN:
152178
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000531
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00269
Gnomad FIN
AF:
0.00198
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00269
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00160
AC:
395
AN:
246130
Hom.:
0
AF XY:
0.00174
AC XY:
234
AN XY:
134286
show subpopulations
Gnomad AFR exome
AF:
0.000197
Gnomad AMR exome
AF:
0.000609
Gnomad ASJ exome
AF:
0.000704
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00171
Gnomad FIN exome
AF:
0.00111
Gnomad NFE exome
AF:
0.00251
Gnomad OTH exome
AF:
0.00182
GnomAD4 exome
AF:
0.00213
AC:
3113
AN:
1460442
Hom.:
6
Cov.:
34
AF XY:
0.00211
AC XY:
1535
AN XY:
726520
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.000626
Gnomad4 ASJ exome
AF:
0.000574
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00170
Gnomad4 FIN exome
AF:
0.00199
Gnomad4 NFE exome
AF:
0.00243
Gnomad4 OTH exome
AF:
0.00172
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00167
AC:
255
AN:
152296
Hom.:
1
Cov.:
32
AF XY:
0.00171
AC XY:
127
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.000529
Gnomad4 AMR
AF:
0.000719
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00269
Gnomad4 FIN
AF:
0.00198
Gnomad4 NFE
AF:
0.00269
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00212
Hom.:
0
Bravo
AF:
0.00129
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00240
EpiControl
AF:
0.00166

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 07, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.47
Cadd
Benign
9.2
Dann
Benign
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs78733835; hg19: chr6-134210976; API