21-42312315-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003226.4(TFF3):​c.230-46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,401,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TFF3
NM_003226.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.150

Publications

0 publications found
Variant links:
Genes affected
TFF3 (HGNC:11757): (trefoil factor 3) Members of the trefoil family are characterized by having at least one copy of the trefoil motif, a 40-amino acid domain that contains three conserved disulfides. They are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are not defined, but they may protect the mucosa from insults, stabilize the mucus layer and affect healing of the epithelium. This gene is expressed in goblet cells of the intestines and colon. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TFF3NM_003226.4 linkc.230-46G>C intron_variant Intron 2 of 2 ENST00000518498.3 NP_003217.4 Q07654

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TFF3ENST00000518498.3 linkc.230-46G>C intron_variant Intron 2 of 2 1 NM_003226.4 ENSP00000430690.2 Q07654
TFF3ENST00000398431.2 linkc.235-46G>C intron_variant Intron 2 of 2 3 ENSP00000381462.2 H7BYT0
TFF3ENST00000489676.1 linkn.203-46G>C intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
152026
Hom.:
0
Cov.:
32
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.14e-7
AC:
1
AN:
1401174
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
690470
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31796
American (AMR)
AF:
0.00
AC:
0
AN:
37804
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21940
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39264
South Asian (SAS)
AF:
0.00
AC:
0
AN:
75430
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49524
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4660
European-Non Finnish (NFE)
AF:
9.23e-7
AC:
1
AN:
1082912
Other (OTH)
AF:
0.00
AC:
0
AN:
57844
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
152026
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74258
African (AFR)
AF:
0.00
AC:
0
AN:
41414
American (AMR)
AF:
0.00
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5172
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10598
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67960
Other (OTH)
AF:
0.00
AC:
0
AN:
2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
2.8
DANN
Benign
0.69
PhyloP100
-0.15

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

Other links and lift over

dbSNP: rs533093; hg19: chr21-43732425; API