12-29563984-C-T

Variant names:

• chr12-29563984-C-T
• rs299487
• NM_001193451.2:c.1533-6984G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001193451.2(TMTC1):​c.1533-6984G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,724 control chromosomes in the GnomAD database, including 25,323 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 (25323 hom., cov: 30)
• Consequence: TMTC1 NM_001193451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMTC1	NM_001193451.2	c.1533-6984G>A		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.1533-6984G>A		intron_variant	Intron 9 of 17	1	NM_001193451.2	ENSP00000442046.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 81985 AN: 151606 Hom.: 25324 Cov.: 30

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.540 AC: 81981 AN: 151724 Hom.: 25323 Cov.: 30 AF XY: 0.543 AC XY: 40258 AN XY: 74142

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.566

Alfa AF: 0.594 Hom.: 4791

Bravo AF: 0.527

Asia WGS AF: 0.576 AC: 2005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.11
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs299487; hg19: chr12-29716917;