Variant 12-29514568-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001193451.2(TMTC1):c.2344C>T(p.Pro782Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TMTC1
NM_001193451.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.95

Variant links:

Genes affected

TMTC1 (HGNC:24099): (transmembrane O-mannosyltransferase targeting cadherins 1) Enables mannosyltransferase activity. Involved in protein O-linked mannosylation. Predicted to be located in endoplasmic reticulum. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMTC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34474683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMTC1	NM_001193451.2 link	c.2344C>T	p.Pro782Ser	missense_variant	16/18	ENST00000539277.6	NP_001180380.1	Q8IUR5-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMTC1	ENST00000539277.6 link	c.2344C>T	p.Pro782Ser	missense_variant	16/18	1	NM_001193451.2	ENSP00000442046.1		Q8IUR5-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251246

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135788

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:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461742

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727164

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:

0.0000126

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000659

Hom.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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 submitter

clinical testing

Ambry Genetics

Aug 20, 2024

The c.2344C>T (p.P782S) alteration is located in exon 16 (coding exon 16) of the TMTC1 gene. This alteration results from a C to T substitution at nucleotide position 2344, causing the proline (P) at amino acid position 782 to be replaced by a serine (S). 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

0.33

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

.;T;.;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Uncertain

0.020

MutationAssessor

Benign

2.0

.;.;.;M

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.1

D;D;D;D

REVEL

Uncertain

0.46

Sift

Benign

0.073

T;D;D;T

Sift4G

Benign

0.60

T;T;T;T

Polyphen

0.66, 0.084

.;P;.;B

Vest4

0.31

MutPred

0.65

.;Loss of methylation at K845 (P = 0.096);.;.;

MVP

0.75

MPC

0.23

ClinPred

0.67

GERP RS

5.1

Varity_R

0.15

gMVP

0.75

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over