rs299454

Variant names:

• chr12-29535564-T-C
• rs299454
• NM_001193451.2:c.1785+645A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMTC1	NM_001193451.2	c.1785+645A>G		intron_variant	Intron 11 of 17	ENST00000539277.6	NP_001180380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMTC1	ENST00000539277.6	c.1785+645A>G		intron_variant	Intron 11 of 17	1	NM_001193451.2	ENSP00000442046.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.550 AC: 11 AN: 20

Other (OTH) AF: 1.00 AC: 2 AN: 2

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

African (AFR) AF: 0.242 AC: 10050 AN: 41482

American (AMR) AF: 0.637 AC: 9713 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2311 AN: 3470

East Asian (EAS) AF: 0.541 AC: 2793 AN: 5160

South Asian (SAS) AF: 0.645 AC: 3102 AN: 4808

European-Finnish (FIN) AF: 0.635 AC: 6707 AN: 10568

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.668 AC: 45391 AN: 67942

Other (OTH) AF: 0.565 AC: 1189 AN: 2104

Alfa AF: 0.632 Hom.: 41095

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
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs299454; hg19: chr12-29688497;