19-54114699-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013342.4(TFPT):​c.25A>G​(p.Thr9Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TFPT
NM_013342.4 missense, splice_region

Scores

4
15
Splicing: ADA: 0.7832
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22
Variant links:
Genes affected
TFPT (HGNC:13630): (TCF3 fusion partner) Predicted to enable DNA binding activity and protein kinase binding activity. Involved in apoptotic signaling pathway. Located in nucleoplasm. Part of Ino80 complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

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=0.14041448).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TFPTNM_013342.4 linkuse as main transcriptc.25A>G p.Thr9Ala missense_variant, splice_region_variant 2/6 ENST00000391759.6
TFPTNM_001321792.2 linkuse as main transcriptc.-3A>G splice_region_variant, 5_prime_UTR_variant 2/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TFPTENST00000391759.6 linkuse as main transcriptc.25A>G p.Thr9Ala missense_variant, splice_region_variant 2/61 NM_013342.4 P1P0C1Z6-1
TFPTENST00000391758.5 linkuse as main transcriptc.-3A>G splice_region_variant, 5_prime_UTR_variant 2/61 P0C1Z6-2
TFPTENST00000391757.1 linkuse as main transcriptc.25A>G p.Thr9Ala missense_variant, splice_region_variant 2/65
TFPTENST00000420715.6 linkuse as main transcriptc.25A>G p.Thr9Ala missense_variant, splice_region_variant, NMD_transcript_variant 2/55

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 20, 2023The c.25A>G (p.T9A) alteration is located in exon 2 (coding exon 2) of the TFPT gene. This alteration results from a A to G substitution at nucleotide position 25, causing the threonine (T) at amino acid position 9 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.45
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
T;.
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.074
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.73
.;T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.20
N;.
MutationTaster
Benign
1.0
D;N;N
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-0.26
N;N
REVEL
Benign
0.040
Sift
Uncertain
0.0090
D;D
Sift4G
Benign
0.16
T;T
Polyphen
0.0
B;.
Vest4
0.32
MutPred
0.23
Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP
0.31
MPC
1.0
ClinPred
0.30
T
GERP RS
3.9
Varity_R
0.078
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.78
dbscSNV1_RF
Benign
0.72
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54618079; API