12-29549252-A-G

Position:

• chr12-29549252-A-G

Variant summary

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

The NM_001193451.2(TMTC1):​c.1676+7605T>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 151,380 control chromosomes in the GnomAD database, including 24,670 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 (24670 hom., cov: 30)
• Consequence: TMTC1 NM_001193451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353

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]

LOC105369714 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMTC1	NM_001193451.2	c.1676+7605T>C		intron_variant		ENST00000539277.6
LOC105369714	XR_007063258.1	n.590-7368A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMTC1	ENST00000539277.6	c.1676+7605T>C		intron_variant		1	NM_001193451.2

Frequencies

GnomAD3 genomes AF: 0.534 AC: 80762 AN: 151260 Hom.: 24672 Cov.: 30

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.667

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: 80758 AN: 151380 Hom.: 24670 Cov.: 30 AF XY: 0.537 AC XY: 39659 AN XY: 73914

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.557

Alfa AF: 0.582 Hom.: 4324

Bravo AF: 0.521

Asia WGS AF: 0.575 AC: 2000 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.8
DANN	Benign	0.91

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: rs299470; hg19: chr12-29702185;