rs7955592

chr12-29625102-G-Achr12-29625102-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.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

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=-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/exons	MANE	UniProt
TMTC1	NM_001193451.2	c.1128+8045C>T		intron_variant		ENST00000539277.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMTC1	ENST00000539277.6	c.1128+8045C>T		intron_variant		1	NM_001193451.2

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

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.245

Alfa AF: 0.234 Hom.: 5905

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

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: rs7955592; hg19: chr12-29778035;