12-29524370-A-G

Position:

• chr12-29524370-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001193451.2(TMTC1):​c.1786-3650T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,044 control chromosomes in the GnomAD database, including 18,221 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (18221 hom., cov: 32)
• Consequence: TMTC1 NM_001193451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMTC1	NM_001193451.2	c.1786-3650T>C		intron_variant		ENST00000539277.6	NP_001180380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMTC1	ENST00000539277.6	c.1786-3650T>C		intron_variant		1	NM_001193451.2	ENSP00000442046.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67862 AN: 151926 Hom.: 18184 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.418

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.447 AC: 67953 AN: 152044 Hom.: 18221 Cov.: 32 AF XY: 0.442 AC XY: 32883 AN XY: 74324

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.419

Alfa AF: 0.316 Hom.: 1150

Bravo AF: 0.459

Asia WGS AF: 0.399 AC: 1385 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.4
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs3910440; hg19: chr12-29677303;