Variant chr12-29583398-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001193451.2(TMTC1):c.1418+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,612,742 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0092 ( 18 hom., cov: 33)

Exomes 𝑓: 0.00089 ( 13 hom. )

Consequence

TMTC1
NM_001193451.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.21

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-29583398-T-C is Benign according to our data. Variant chr12-29583398-T-C is described in ClinVar as [Benign]. Clinvar id is 785397.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00916 (1396/152370) while in subpopulation AFR AF= 0.0318 (1322/41576). AF 95% confidence interval is 0.0304. There are 18 homozygotes in gnomad4. There are 666 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMTC1	NM_001193451.2 linkuse as main transcript	c.1418+9A>G		intron_variant		ENST00000539277.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMTC1	ENST00000539277.6 linkuse as main transcript	c.1418+9A>G		intron_variant		1	NM_001193451.2		Q8IUR5-5

Frequencies

GnomAD3 genomes

AF:

0.00903

AC:

1375

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00240

AC:

599

AN:

249872

Hom.:

AF XY:

0.00171

AC XY:

231

AN XY:

135008

show subpopulations

Gnomad AFR exome

AF:

0.0325

Gnomad AMR exome

AF:

0.00166

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000986

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000887

AC:

1296

AN:

1460372

Hom.:

Cov.:

AF XY:

0.000789

AC XY:

573

AN XY:

726444

show subpopulations

Gnomad4 AFR exome

AF:

0.0303

Gnomad4 AMR exome

AF:

0.00184

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.00232

GnomAD4 genome

AF:

0.00916

AC:

1396

AN:

152370

Hom.:

Cov.:

AF XY:

0.00894

AC XY:

666

AN XY:

74528

show subpopulations

Gnomad4 AFR

AF:

0.0318

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00483

Hom.:

Bravo

AF:

0.0104

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0000547

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.067

DANN

Benign

0.73

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