17-15328024-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_031898.3(TEKT3):​c.631G>T​(p.Val211Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TEKT3
NM_031898.3 missense

Scores

9
6
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.76
Variant links:
Genes affected
TEKT3 (HGNC:14293): (tektin 3) This gene product belongs to the tektin family of proteins. Tektins comprise a family of filament-forming proteins that are coassembled with tubulins to form ciliary and flagellar microtubules. The exact function of this gene is not known. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.963

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TEKT3NM_031898.3 linkc.631G>T p.Val211Phe missense_variant 4/9 ENST00000395930.6 NP_114104.1 Q9BXF9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TEKT3ENST00000395930.6 linkc.631G>T p.Val211Phe missense_variant 4/91 NM_031898.3 ENSP00000379263.1 Q9BXF9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461774
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727188
show subpopulations
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

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 GeneticsSep 14, 2021The c.631G>T (p.V211F) alteration is located in exon 4 (coding exon 2) of the TEKT3 gene. This alteration results from a G to T substitution at nucleotide position 631, causing the valine (V) at amino acid position 211 to be replaced by a phenylalanine (F). 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
Pathogenic
0.71
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T;T;T
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
.;D;D
M_CAP
Benign
0.062
D
MetaRNN
Pathogenic
0.96
D;D;D
MetaSVM
Benign
-0.82
T
MutationAssessor
Pathogenic
3.9
H;H;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Pathogenic
-4.9
D;D;D
REVEL
Uncertain
0.58
Sift
Uncertain
0.0010
D;D;D
Sift4G
Pathogenic
0.0
D;D;.
Polyphen
1.0
D;D;.
Vest4
0.92
MutPred
0.87
Loss of stability (P = 0.0272);Loss of stability (P = 0.0272);.;
MVP
0.49
MPC
0.74
ClinPred
1.0
D
GERP RS
5.2
Varity_R
0.96
gMVP
0.79

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: chr17-15231341; API