rs200497052

Variant summary

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

The NM_013342.4(TFPT):​c.590G>C​(p.Arg197Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000712 in 1,405,270 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: not found (cov: 32)
Exomes š‘“: 7.1e-7 ( 0 hom. )

Consequence

TFPT
NM_013342.4 missense

Scores

2
3
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.88
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]
NDUFA3 (HGNC:7686): (NADH:ubiquinone oxidoreductase subunit A3) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion. Part of mitochondrial respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.1767863).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TFPTNM_013342.4 linkc.590G>C p.Arg197Pro missense_variant Exon 5 of 6 ENST00000391759.6 NP_037474.1 P0C1Z6-1A0A024R4Q5
TFPTNM_001321792.2 linkc.563G>C p.Arg188Pro missense_variant Exon 5 of 6 NP_001308721.1 P0C1Z6-2
TFPTXM_005278261.2 linkc.230G>C p.Arg77Pro missense_variant Exon 4 of 5 XP_005278318.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TFPTENST00000391759.6 linkc.590G>C p.Arg197Pro missense_variant Exon 5 of 6 1 NM_013342.4 ENSP00000375639.1 P0C1Z6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.12e-7
AC:
1
AN:
1405270
Hom.:
0
Cov.:
33
AF XY:
0.00000144
AC XY:
1
AN XY:
693680
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000455
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Pathogenic
0.39
D
BayesDel_noAF
Benign
-0.21
CADD
Benign
22
DANN
Uncertain
1.0
Eigen
Uncertain
0.20
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.063
D
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-0.94
T
PROVEAN
Benign
2.1
N
REVEL
Benign
0.070
Sift
Pathogenic
0.0
D
Vest4
0.44
MutPred
0.19
Gain of MoRF binding (P = 0.0545);
MVP
0.52
ClinPred
0.86
D
GERP RS
5.0

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54611385; API