chr12-29582100-G-A

Variant names:

• chr12-29582100-G-A
• rs10492312
• NM_001193451.2:c.1418+1307C>T

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+1307C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,040 control chromosomes in the GnomAD database, including 12,803 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 0.40 (12803 hom., cov: 33)
• Consequence: TMTC1 NM_001193451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMTC1	NM_001193451.2	MANE Select	c.1418+1307C>T		intron	N/A	NP_001180380.1
	TMTC1	NM_001367875.2		c.1604+1307C>T		intron	N/A	NP_001354804.1
	TMTC1	NM_175861.3		c.1094+1307C>T		intron	N/A	NP_787057.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMTC1	ENST00000539277.6	TSL:1 MANE Select	c.1418+1307C>T		intron	N/A	ENSP00000442046.1
	TMTC1	ENST00000256062.9	TSL:1	c.1094+1307C>T		intron	N/A	ENSP00000256062.5
	TMTC1	ENST00000551659.6	TSL:5	c.1604+1307C>T		intron	N/A	ENSP00000448112.1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60051 AN: 151922 Hom.: 12759 Cov.: 33

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.396 AC: 60150 AN: 152040 Hom.: 12803 Cov.: 33 AF XY: 0.395 AC XY: 29376 AN XY: 74300

African (AFR) AF: 0.551 AC: 22844 AN: 41468

American (AMR) AF: 0.333 AC: 5087 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1074 AN: 3466

East Asian (EAS) AF: 0.456 AC: 2360 AN: 5170

South Asian (SAS) AF: 0.352 AC: 1698 AN: 4826

European-Finnish (FIN) AF: 0.371 AC: 3918 AN: 10552

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21958 AN: 67970

Other (OTH) AF: 0.382 AC: 806 AN: 2112

Alfa AF: 0.379 Hom.: 1462

Bravo AF: 0.399

Asia WGS AF: 0.421 AC: 1460 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.77
PhyloP100		-0.82
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: rs10492312; hg19: chr12-29735033;