19-15011223-C-T

Variant summary

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

The NM_173482.3(TEKTL1):​c.398C>T​(p.Ala133Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000136 in 1,475,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

TEKTL1
NM_173482.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.130
Variant links:
Genes affected
TEKTL1 (HGNC:26866): (tektin like 1) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]
SLC1A6 (HGNC:10944): (solute carrier family 1 member 6) Predicted to enable high-affinity glutamate transmembrane transporter activity. Involved in neurotransmitter uptake. Located in intermediate filament cytoskeleton and plasma membrane. [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=0.14478648).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TEKTL1NM_173482.3 linkc.398C>T p.Ala133Val missense_variant Exon 1 of 7 ENST00000292574.4 NP_775753.2 Q8IYK2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC105ENST00000292574.4 linkc.398C>T p.Ala133Val missense_variant Exon 1 of 7 1 NM_173482.3 ENSP00000292574.2 Q8IYK2
SLC1A6ENST00000595863.1 linkc.-8+11681G>A intron_variant Intron 1 of 2 3 ENSP00000469551.1 M0QY32

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151804
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.55e-7
AC:
1
AN:
1323816
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
648904
show subpopulations
Gnomad4 AFR exome
AF:
0.0000378
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151804
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74136
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 12, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.398C>T (p.A133V) alteration is located in exon 1 (coding exon 1) of the CCDC105 gene. This alteration results from a C to T substitution at nucleotide position 398, causing the alanine (A) at amino acid position 133 to be replaced by a valine (V). 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
0.13
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.00051
T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.42
FATHMM_MKL
Benign
0.047
N
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.31
N
REVEL
Benign
0.053
Sift
Benign
0.75
T
Sift4G
Benign
0.46
T
Polyphen
0.77
P
Vest4
0.33
MutPred
0.25
Loss of helix (P = 0.0558);
MVP
0.18
MPC
0.54
ClinPred
0.59
D
GERP RS
1.2
Varity_R
0.027
gMVP
0.14

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: rs1240287216; hg19: chr19-15122035; API