rs10492312

Positions:

• chr12-29582100-G-A
• chr12-29582100-G-C

Variant summary

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

The NM_001193451.2(TMTC1):​c.1418+1307C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,040 control chromosomes in the GnomAD database, including 12,803 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 0.40 (12803 hom., cov: 33)
• Consequence: TMTC1 NM_001193451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816

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]

TMTC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMTC1	NM_001193451.2	c.1418+1307C>T		intron_variant		ENST00000539277.6	NP_001180380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMTC1	ENST00000539277.6	c.1418+1307C>T		intron_variant		1	NM_001193451.2	ENSP00000442046.1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60051 AN: 151922 Hom.: 12759 Cov.: 33

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.396 AC: 60150 AN: 152040 Hom.: 12803 Cov.: 33 AF XY: 0.395 AC XY: 29376 AN XY: 74300

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.382

Alfa AF: 0.371 Hom.: 1332

Bravo AF: 0.399

Asia WGS AF: 0.421 AC: 1460 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.77

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: rs10492312; hg19: chr12-29735033;