12-29583178-C-G

Variant names:

• chr12-29583178-C-G
• rs1326758
• NM_001193451.2:c.1418+229G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001193451.2(TMTC1):​c.1418+229G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,908 control chromosomes in the GnomAD database, including 15,099 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 0.42 (15099 hom., cov: 32)
• Consequence: TMTC1 NM_001193451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193451.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMTC1	NM_001193451.2	MANE Select	c.1418+229G>C		intron	N/A	NP_001180380.1	Q8IUR5-5
	TMTC1	NM_001367875.2		c.1604+229G>C		intron	N/A	NP_001354804.1	F8VTQ9
	TMTC1	NM_175861.3		c.1094+229G>C		intron	N/A	NP_787057.2	Q8IUR5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMTC1	ENST00000539277.6	TSL:1 MANE Select	c.1418+229G>C		intron	N/A	ENSP00000442046.1	Q8IUR5-5
	TMTC1	ENST00000256062.9	TSL:1	c.1094+229G>C		intron	N/A	ENSP00000256062.5	Q8IUR5-1
	TMTC1	ENST00000904147.1		c.1670+229G>C		intron	N/A	ENSP00000574206.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63379 AN: 151790 Hom.: 15079 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.418 AC: 63434 AN: 151908 Hom.: 15099 Cov.: 32 AF XY: 0.413 AC XY: 30643 AN XY: 74242

African (AFR) AF: 0.653 AC: 27052 AN: 41444

American (AMR) AF: 0.316 AC: 4822 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3466

East Asian (EAS) AF: 0.390 AC: 2015 AN: 5172

South Asian (SAS) AF: 0.275 AC: 1318 AN: 4796

European-Finnish (FIN) AF: 0.357 AC: 3762 AN: 10528

Middle Eastern (MID) AF: 0.337 AC: 97 AN: 288

European-Non Finnish (NFE) AF: 0.327 AC: 22185 AN: 67940

Other (OTH) AF: 0.393 AC: 829 AN: 2110

Alfa AF: 0.219 Hom.: 447

Bravo AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.77
DANN	Benign	0.68
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1326758; hg19: chr12-29736111;