rs299454

Positions:

• chr12-29535564-T-C

Variant summary

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

The NM_001193451.2(TMTC1):​c.1785+645A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,012 control chromosomes in the GnomAD database, including 25,022 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 (25016 hom., cov: 32)
  • Exomes 𝑓: 0.63 (6 hom.)
• Consequence: TMTC1 NM_001193451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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=-0.76).
• 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	UniProt
TMTC1	NM_001193451.2	c.1785+645A>G		intron_variant		ENST00000539277.6
LOC105369714	XR_007063258.1	n.589+2037T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMTC1	ENST00000539277.6	c.1785+645A>G		intron_variant		1	NM_001193451.2

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82018 AN: 151870 Hom.: 25017 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.565

GnomAD4 exome AF: 0.625 AC: 15 AN: 24 Hom.: 6 Cov.: 0 AF XY: 0.625 AC XY: 10 AN XY: 16

Gnomad4 AMR exome AF: 1.00

Gnomad4 NFE exome AF: 0.550

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.540 AC: 82021 AN: 151988 Hom.: 25016 Cov.: 32 AF XY: 0.542 AC XY: 40301 AN XY: 74288

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.565

Alfa AF: 0.648 Hom.: 32898

Bravo AF: 0.528

Asia WGS AF: 0.571 AC: 1988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.5
DANN	Benign	0.84

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: rs299454; hg19: chr12-29688497;