rs765949011

Variant names:

• chr21-42350918-C-A
• rs765949011
• NM_005423.5:c.40G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-42350918-C-A
• chr21-42350918-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005423.5(TFF2):​c.40G>T​(p.Val14Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V14I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TFF2 NM_005423.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

Genes affected

TFF2 (HGNC:11756): (trefoil factor 2) 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. The encoded protein inhibits gastric acid secretion. 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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24257004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFF2	NM_005423.5	c.40G>T	p.Val14Phe	missense_variant	Exon 1 of 4	ENST00000291526.5	NP_005414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFF2	ENST00000291526.5	c.40G>T	p.Val14Phe	missense_variant	Exon 1 of 4	1	NM_005423.5	ENSP00000291526.4
TFF2	ENST00000463771.5	n.80G>T		non_coding_transcript_exon_variant	Exon 1 of 4	5
TFF2	ENST00000475297.1	n.77G>T		non_coding_transcript_exon_variant	Exon 1 of 5	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461586 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727110

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.87
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.098
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.026	D
Polyphen		0.87	P
Vest4		0.14
MutPred		0.36		Gain of disorder (P = 0.1117);
MVP		0.24
MPC		0.55
ClinPred		0.16	T
GERP RS		-2.5
Varity_R		0.062
gMVP		0.56

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

Other links and lift over

dbSNP: rs765949011; hg19: chr21-43771027;