12-29719385-T-G

Variant names:

• chr12-29719385-T-G
• rs16934812
• NM_001193451.2:c.938+32281A>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.938+32281A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,192 control chromosomes in the GnomAD database, including 1,309 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 0.12 (1309 hom., cov: 32)
• Consequence: TMTC1 NM_001193451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.728
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMTC1	NM_001193451.2	c.938+32281A>C		intron_variant	Intron 5 of 17	ENST00000539277.6	NP_001180380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMTC1	ENST00000539277.6	c.938+32281A>C		intron_variant	Intron 5 of 17	1	NM_001193451.2	ENSP00000442046.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18661 AN: 152074 Hom.: 1307 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0971

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.123 AC: 18676 AN: 152192 Hom.: 1309 Cov.: 32 AF XY: 0.125 AC XY: 9283 AN XY: 74418

African (AFR) AF: 0.100 AC: 4155 AN: 41530

American (AMR) AF: 0.224 AC: 3428 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 315 AN: 3470

East Asian (EAS) AF: 0.116 AC: 601 AN: 5176

South Asian (SAS) AF: 0.0978 AC: 471 AN: 4816

European-Finnish (FIN) AF: 0.128 AC: 1359 AN: 10604

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8014 AN: 68000

Other (OTH) AF: 0.119 AC: 252 AN: 2110

Alfa AF: 0.121 Hom.: 3860

Bravo AF: 0.133

Asia WGS AF: 0.0920 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.76
PhyloP100		0.73
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: rs16934812; hg19: chr12-29872318;