12-88153276-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_181783.4(TMTC3):​c.190-15G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000559 in 1,591,470 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

TMTC3
NM_181783.4 splice_polypyrimidine_tract, intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0420
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
Variant 12-88153276-G-A is Benign according to our data. Variant chr12-88153276-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1534417.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TMTC3NM_181783.4 linkuse as main transcriptc.190-15G>A splice_polypyrimidine_tract_variant, intron_variant ENST00000266712.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TMTC3ENST00000266712.11 linkuse as main transcriptc.190-15G>A splice_polypyrimidine_tract_variant, intron_variant 1 NM_181783.4 P1Q6ZXV5-2
TMTC3ENST00000547034.5 linkuse as main transcriptc.190-15G>A splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant 1
TMTC3ENST00000549011.5 linkuse as main transcriptc.190-15G>A splice_polypyrimidine_tract_variant, intron_variant 4
TMTC3ENST00000551088.1 linkuse as main transcriptc.190-1012G>A intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152018
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000377
AC:
9
AN:
238842
Hom.:
0
AF XY:
0.0000464
AC XY:
6
AN XY:
129236
show subpopulations
Gnomad AFR exome
AF:
0.0000626
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:
0.0000646
Gnomad OTH exome
AF:
0.000174
GnomAD4 exome
AF:
0.0000556
AC:
80
AN:
1439452
Hom.:
0
Cov.:
30
AF XY:
0.0000503
AC XY:
36
AN XY:
715682
show subpopulations
Gnomad4 AFR exome
AF:
0.0000610
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:
0.0000683
Gnomad4 OTH exome
AF:
0.0000506
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152018
Hom.:
0
Cov.:
32
AF XY:
0.0000539
AC XY:
4
AN XY:
74250
show subpopulations
Gnomad4 AFR
AF:
0.000121
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:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000145
Hom.:
0
Bravo
AF:
0.0000491

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 20, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
CADD
Benign
12
DANN
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs376826681; hg19: chr12-88547053; API