chr19-15011369-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_173482.3(TEKTL1):​c.544C>T​(p.Arg182Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TEKTL1
NM_173482.3 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.750
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TEKTL1NM_173482.3 linkc.544C>T p.Arg182Trp 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.544C>T p.Arg182Trp missense_variant Exon 1 of 7 1 NM_173482.3 ENSP00000292574.2 Q8IYK2
SLC1A6ENST00000595863.1 linkc.-8+11535G>A intron_variant Intron 1 of 2 3 ENSP00000469551.1 M0QY32

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1294406
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
630112
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 03, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.544C>T (p.R182W) 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 544, causing the arginine (R) at amino acid position 182 to be replaced by a tryptophan (W). 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
0.50
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.042
T
Eigen
Benign
0.0063
Eigen_PC
Benign
-0.13
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.061
D
MetaRNN
Pathogenic
0.82
D
MetaSVM
Benign
-0.82
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Uncertain
0.57
T
PROVEAN
Pathogenic
-8.0
D
REVEL
Uncertain
0.37
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.85
MutPred
0.51
Loss of disorder (P = 0.0023);
MVP
0.12
MPC
1.2
ClinPred
1.0
D
GERP RS
1.5
Varity_R
0.80
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr19-15122181; COSMIC: COSV52964736; COSMIC: COSV52964736; API