12-29556157-C-T

Position:

• chr12-29556157-C-T

Variant summary

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

The ENST00000539277.6(TMTC1):​c.1676+700G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 151,874 control chromosomes in the GnomAD database, including 25,173 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 (25173 hom., cov: 31)
• Consequence: TMTC1 ENST00000539277.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMTC1	NM_001193451.2	c.1676+700G>A		intron_variant		ENST00000539277.6	NP_001180380.1
LOC105369714	XR_007063258.1	n.590-463C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMTC1	ENST00000539277.6	c.1676+700G>A		intron_variant		1	NM_001193451.2	ENSP00000442046

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82523 AN: 151756 Hom.: 25170 Cov.: 31

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.543 AC: 82524 AN: 151874 Hom.: 25173 Cov.: 31 AF XY: 0.546 AC XY: 40513 AN XY: 74236

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.566

Alfa AF: 0.572 Hom.: 5007

Bravo AF: 0.530

Asia WGS AF: 0.573 AC: 1995 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.83

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: rs299479; hg19: chr12-29709090;