16-10635804-G-A

Variant summary

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

The NM_144674.2(TEKT5):​c.1201C>T​(p.Arg401Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,988 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: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TEKT5
NM_144674.2 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74
Variant links:
Genes affected
TEKT5 (HGNC:26554): (tektin 5) Predicted to be involved in cilium assembly and cilium movement involved in cell motility. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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, 0.971

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TEKT5NM_144674.2 linkuse as main transcriptc.1201C>T p.Arg401Cys missense_variant 6/7 ENST00000283025.7 NP_653275.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TEKT5ENST00000283025.7 linkuse as main transcriptc.1201C>T p.Arg401Cys missense_variant 6/71 NM_144674.2 ENSP00000283025 P1
TEKT5ENST00000576638.1 linkuse as main transcriptc.520C>T p.Arg174Cys missense_variant 5/53 ENSP00000458802
TEKT5ENST00000574923.1 linkuse as main transcriptn.184C>T non_coding_transcript_exon_variant 2/32

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152202
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251204
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135770
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461786
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152202
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsApr 17, 2024The c.1201C>T (p.R401C) alteration is located in exon 6 (coding exon 6) of the TEKT5 gene. This alteration results from a C to T substitution at nucleotide position 1201, causing the arginine (R) at amino acid position 401 to be replaced by a cysteine (C). 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
Uncertain
0.54
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.10
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.24
T;.
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.97
D;D
MetaSVM
Benign
-0.61
T
MutationAssessor
Pathogenic
3.8
H;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-7.1
D;.
REVEL
Uncertain
0.45
Sift
Pathogenic
0.0
D;.
Sift4G
Pathogenic
0.0010
D;.
Polyphen
1.0
D;.
Vest4
0.92
MutPred
0.94
Loss of MoRF binding (P = 0.0053);.;
MVP
0.45
MPC
0.23
ClinPred
1.0
D
GERP RS
4.6
Varity_R
0.75
gMVP
0.68

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: rs752263208; hg19: chr16-10729661; API