12-29562183-C-G

Variant names:

• chr12-29562183-C-G
• rs148898
• NM_001193451.2:c.1533-5183G>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.1533-5183G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,014 control chromosomes in the GnomAD database, including 24,698 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 0.53 (24698 hom., cov: 33)
• Consequence: TMTC1 NM_001193451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• 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]

LOC124902909 (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 = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMTC1	NM_001193451.2	c.1533-5183G>C		intron_variant	Intron 9 of 17	ENST00000539277.6	NP_001180380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMTC1	ENST00000539277.6	c.1533-5183G>C		intron_variant	Intron 9 of 17	1	NM_001193451.2	ENSP00000442046.1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81057 AN: 151896 Hom.: 24698 Cov.: 33

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.533 AC: 81054 AN: 152014 Hom.: 24698 Cov.: 33 AF XY: 0.536 AC XY: 39829 AN XY: 74312

African (AFR) AF: 0.223 AC: 9248 AN: 41436

American (AMR) AF: 0.635 AC: 9712 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2304 AN: 3472

East Asian (EAS) AF: 0.548 AC: 2825 AN: 5156

South Asian (SAS) AF: 0.644 AC: 3114 AN: 4834

European-Finnish (FIN) AF: 0.631 AC: 6664 AN: 10554

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45244 AN: 67958

Other (OTH) AF: 0.557 AC: 1178 AN: 2114

Alfa AF: 0.466 Hom.: 1531

Bravo AF: 0.521

Asia WGS AF: 0.572 AC: 1992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.15
DANN	Benign	0.34
PhyloP100		-1.3
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: rs148898; hg19: chr12-29715116;