NM_001193451.2:c.1128+8045C>T

Variant names:

• chr12-29625102-G-A
• rs7955592
• NM_001193451.2:c.1128+8045C>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.1128+8045C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,024 control chromosomes in the GnomAD database, including 6,041 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 0.27 (6041 hom., cov: 32)
• Consequence: TMTC1 NM_001193451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 10 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMTC1	NM_001193451.2	c.1128+8045C>T		intron_variant	Intron 6 of 17	ENST00000539277.6	NP_001180380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMTC1	ENST00000539277.6	c.1128+8045C>T		intron_variant	Intron 6 of 17	1	NM_001193451.2	ENSP00000442046.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41597 AN: 151904 Hom.: 6024 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.274 AC: 41656 AN: 152024 Hom.: 6041 Cov.: 32 AF XY: 0.272 AC XY: 20232 AN XY: 74308

African (AFR) AF: 0.366 AC: 15157 AN: 41428

American (AMR) AF: 0.259 AC: 3952 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 750 AN: 3464

East Asian (EAS) AF: 0.150 AC: 778 AN: 5172

South Asian (SAS) AF: 0.245 AC: 1180 AN: 4814

European-Finnish (FIN) AF: 0.272 AC: 2871 AN: 10572

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16211 AN: 67980

Other (OTH) AF: 0.245 AC: 516 AN: 2110

Alfa AF: 0.240 Hom.: 8638

Bravo AF: 0.275

Asia WGS AF: 0.200 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.0
DANN	Benign	0.49
PhyloP100		-0.27
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: rs7955592; hg19: chr12-29778035;