12-29556157-C-T

Variant names:

• chr12-29556157-C-T
• rs299479
• NM_001193451.2:c.1676+700G>A

Variant summary

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

The NM_001193451.2(TMTC1):​c.1676+700G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 151,874 control chromosomes in the GnomAD database, including 25,173 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 0.54 (25173 hom., cov: 31)
• Consequence: TMTC1 NM_001193451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• 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]

LOC105369714 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 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.1676+700G>A		intron	N/A	NP_001180380.1
	TMTC1	NM_001367875.2		c.1862+700G>A		intron	N/A	NP_001354804.1
	TMTC1	NM_175861.3		c.1352+700G>A		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.1676+700G>A		intron	N/A	ENSP00000442046.1
	TMTC1	ENST00000256062.9	TSL:1	c.1352+700G>A		intron	N/A	ENSP00000256062.5
	TMTC1	ENST00000551659.6	TSL:5	c.1862+700G>A		intron	N/A	ENSP00000448112.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82523 AN: 151756 Hom.: 25170 Cov.: 31

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.543 AC: 82524 AN: 151874 Hom.: 25173 Cov.: 31 AF XY: 0.546 AC XY: 40513 AN XY: 74236

African (AFR) AF: 0.253 AC: 10467 AN: 41358

American (AMR) AF: 0.638 AC: 9740 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2311 AN: 3464

East Asian (EAS) AF: 0.548 AC: 2837 AN: 5178

South Asian (SAS) AF: 0.645 AC: 3103 AN: 4808

European-Finnish (FIN) AF: 0.635 AC: 6696 AN: 10538

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.668 AC: 45415 AN: 67954

Other (OTH) AF: 0.566 AC: 1195 AN: 2110

Alfa AF: 0.578 Hom.: 9642

Bravo AF: 0.530

Asia WGS AF: 0.573 AC: 1995 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.83
PhyloP100		-1.7
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: rs299479; hg19: chr12-29709090;