21-42312315-C-T

Variant names:

• chr21-42312315-C-T
• rs533093
• NM_003226.4:c.230-46G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003226.4(TFF3):​c.230-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,551,714 control chromosomes in the GnomAD database, including 116,762 homozygotes. 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 0.30 (8239 hom., cov: 32)
  • Exomes 𝑓: 0.38 (108523 hom.)
• Consequence: TFF3 NM_003226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003226.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFF3	NM_003226.4	MANE Select	c.230-46G>A		intron	N/A	NP_003217.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFF3	ENST00000518498.3	TSL:1 MANE Select	c.230-46G>A		intron	N/A	ENSP00000430690.2
	TFF3	ENST00000398431.2	TSL:3	c.235-46G>A		intron	N/A	ENSP00000381462.2
	TFF3	ENST00000489676.1	TSL:2	n.203-46G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45277 AN: 151978 Hom.: 8242 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.0499

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.323

GnomAD2 exomes AF: 0.321 AC: 63020 AN: 196122 AF XY: 0.331

Gnomad AFR exome AF: 0.0967

Gnomad AMR exome AF: 0.295

Gnomad ASJ exome AF: 0.401

Gnomad EAS exome AF: 0.0521

Gnomad FIN exome AF: 0.356

Gnomad NFE exome AF: 0.407

Gnomad OTH exome AF: 0.365

GnomAD4 exome AF: 0.384 AC: 537732 AN: 1399618 Hom.: 108523 Cov.: 34 AF XY: 0.383 AC XY: 264468 AN XY: 689762

African (AFR) AF: 0.0883 AC: 2806 AN: 31784

American (AMR) AF: 0.304 AC: 11482 AN: 37756

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 8882 AN: 21928

East Asian (EAS) AF: 0.0450 AC: 1765 AN: 39262

South Asian (SAS) AF: 0.327 AC: 24687 AN: 75386

European-Finnish (FIN) AF: 0.355 AC: 17541 AN: 49480

Middle Eastern (MID) AF: 0.347 AC: 1613 AN: 4646

European-Non Finnish (NFE) AF: 0.415 AC: 448436 AN: 1081588

Other (OTH) AF: 0.355 AC: 20520 AN: 57788

GnomAD4 genome AF: 0.298 AC: 45277 AN: 152096 Hom.: 8239 Cov.: 32 AF XY: 0.294 AC XY: 21868 AN XY: 74358

African (AFR) AF: 0.104 AC: 4306 AN: 41526

American (AMR) AF: 0.331 AC: 5050 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1406 AN: 3468

East Asian (EAS) AF: 0.0502 AC: 259 AN: 5160

South Asian (SAS) AF: 0.330 AC: 1590 AN: 4822

European-Finnish (FIN) AF: 0.351 AC: 3718 AN: 10588

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27684 AN: 67940

Other (OTH) AF: 0.319 AC: 674 AN: 2110

Alfa AF: 0.355 Hom.: 2350

Bravo AF: 0.287

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.86
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs533093; hg19: chr21-43732425;