4-48086629-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003328.3(TXK):​c.793G>A​(p.Glu265Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

TXK
NM_003328.3 missense

Scores

14
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40
Variant links:
Genes affected
TXK (HGNC:12434): (TXK tyrosine kinase) Predicted to enable non-membrane spanning protein tyrosine kinase activity. Involved in positive regulation of interferon-gamma-mediated signaling pathway; positive regulation of macromolecule metabolic process; and protein autophosphorylation. Located in cytoplasm and nucleus. [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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28707027).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TXKNM_003328.3 linkc.793G>A p.Glu265Lys missense_variant 10/15 ENST00000264316.9 NP_003319.2 P42681

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TXKENST00000264316.9 linkc.793G>A p.Glu265Lys missense_variant 10/151 NM_003328.3 ENSP00000264316.4 P42681
TXKENST00000506073.2 linkc.793G>A p.Glu265Lys missense_variant 9/143 ENSP00000422798.2 E7EQN8

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152128
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
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:
0.00316
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000240
AC:
6
AN:
249982
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135068
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000349
AC:
51
AN:
1460884
Hom.:
0
Cov.:
32
AF XY:
0.0000303
AC XY:
22
AN XY:
726706
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
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:
0.0000414
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.0000806
AC XY:
6
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000116
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.000273
EpiControl
AF:
0.0000593

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 GeneticsJul 15, 2021The c.793G>A (p.E265K) alteration is located in exon 10 (coding exon 10) of the TXK gene. This alteration results from a G to A substitution at nucleotide position 793, causing the glutamic acid (E) at amino acid position 265 to be replaced by a lysine (K). 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
0.18
BayesDel_addAF
Benign
-0.060
T
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.63
D
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.29
T
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Uncertain
2.7
M
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.5
D
REVEL
Uncertain
0.44
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0080
D
Polyphen
0.38
B
Vest4
0.34
MVP
0.88
MPC
0.18
ClinPred
0.27
T
GERP RS
5.1
Varity_R
0.71
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs531077454; hg19: chr4-48088646; API