chr12-88148318-G-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_181783.4(TMTC3):​c.3G>A​(p.Met1?) variant causes a start lost change involving the alteration of a 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 Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

TMTC3
NM_181783.4 start_lost

Scores

4
8
4

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.69
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-88148318-G-A is Pathogenic according to our data. Variant chr12-88148318-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 372277.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TMTC3NM_181783.4 linkuse as main transcriptc.3G>A p.Met1? start_lost 2/14 ENST00000266712.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TMTC3ENST00000266712.11 linkuse as main transcriptc.3G>A p.Met1? start_lost 2/141 NM_181783.4 P1Q6ZXV5-2
TMTC3ENST00000547034.5 linkuse as main transcriptc.3G>A p.Met1? start_lost, NMD_transcript_variant 2/121
TMTC3ENST00000549011.5 linkuse as main transcriptc.3G>A p.Met1? start_lost 2/44
TMTC3ENST00000551088.1 linkuse as main transcriptc.3G>A p.Met1? start_lost 2/53

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Lissencephaly 8 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMDec 17, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.27
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.022
T;.;T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.97
D;D;D
MetaSVM
Benign
-0.70
T
MutationTaster
Benign
1.0
D
PROVEAN
Benign
-1.4
N;N;N
REVEL
Uncertain
0.40
Sift
Uncertain
0.016
D;D;D
Sift4G
Uncertain
0.045
D;D;D
Polyphen
0.42
.;B;.
Vest4
0.96
MutPred
0.97
Gain of catalytic residue at L6 (P = 0.0017);Gain of catalytic residue at L6 (P = 0.0017);Gain of catalytic residue at L6 (P = 0.0017);
MVP
0.73
ClinPred
0.99
D
GERP RS
5.3
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.32
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.32
Position offset: -30

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: rs1057517698; hg19: chr12-88542095; API