12-88148344-C-T

Variant summary

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

The NM_181783.4(TMTC3):​c.29C>T​(p.Thr10Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TMTC3
NM_181783.4 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37
Variant links:
Genes affected
TMTC3 (HGNC:26899): (transmembrane O-mannosyltransferase targeting cadherins 3) This gene encodes a protein that belongs to the transmembrane and tetratricopeptide repeat-containing protein family. [provided by RefSeq, May 2010]

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=0.094840676).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMTC3NM_181783.4 linkc.29C>T p.Thr10Ile missense_variant Exon 2 of 14 ENST00000266712.11 NP_861448.2 Q6ZXV5-2A8K321

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMTC3ENST00000266712.11 linkc.29C>T p.Thr10Ile missense_variant Exon 2 of 14 1 NM_181783.4 ENSP00000266712.6 Q6ZXV5-2
TMTC3ENST00000547034.5 linkn.29C>T non_coding_transcript_exon_variant Exon 2 of 12 1 ENSP00000448733.1 F8VRY4
TMTC3ENST00000549011.5 linkc.29C>T p.Thr10Ile missense_variant Exon 2 of 4 4 ENSP00000447640.1 F8W044
TMTC3ENST00000551088.1 linkc.29C>T p.Thr10Ile missense_variant Exon 2 of 5 3 ENSP00000448566.1 F8VR71

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250658
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135458
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:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1460626
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726608
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Jan 24, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.29C>T (p.T10I) alteration is located in exon 2 (coding exon 1) of the TMTC3 gene. This alteration results from a C to T substitution at nucleotide position 29, causing the threonine (T) at amino acid position 10 to be replaced by an isoleucine (I). 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
BayesDel_addAF
Benign
-0.082
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
18
DANN
Uncertain
0.97
DEOGEN2
Benign
0.0069
T;.;T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.63
D
LIST_S2
Benign
0.71
T;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.095
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.20
.;N;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
0.32
N;N;N
REVEL
Benign
0.068
Sift
Benign
0.38
T;T;T
Sift4G
Benign
0.41
T;T;T
Polyphen
0.0040
.;B;.
Vest4
0.17
MutPred
0.38
Gain of catalytic residue at V15 (P = 0);Gain of catalytic residue at V15 (P = 0);Gain of catalytic residue at V15 (P = 0);
MVP
0.51
MPC
0.34
ClinPred
0.069
T
GERP RS
3.4
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1565941864; hg19: chr12-88542121; API