chr12-29562183-C-G

Position:

• chr12-29562183-C-G

Variant summary

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

The ENST00000539277.6(TMTC1):​c.1533-5183G>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 152,014 control chromosomes in the GnomAD database, including 24,698 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 (24698 hom., cov: 33)
• Consequence: TMTC1 ENST00000539277.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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]

LOC124902909 (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 = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMTC1	NM_001193451.2	c.1533-5183G>C		intron_variant		ENST00000539277.6	NP_001180380.1
LOC124902909	XR_007063259.1	n.222-58C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMTC1	ENST00000539277.6	c.1533-5183G>C		intron_variant		1	NM_001193451.2	ENSP00000442046

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81057 AN: 151896 Hom.: 24698 Cov.: 33

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.666

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: 81054 AN: 152014 Hom.: 24698 Cov.: 33 AF XY: 0.536 AC XY: 39829 AN XY: 74312

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.557

Alfa AF: 0.466 Hom.: 1531

Bravo AF: 0.521

Asia WGS AF: 0.572 AC: 1992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.15
DANN	Benign	0.34

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: rs148898; hg19: chr12-29715116;