rs299467

Variant names:

• chr12-29548357-A-G
• rs299467
• NM_001193451.2:c.1676+8500T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-29548357-A-G
• chr12-29548357-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001193451.2(TMTC1):​c.1676+8500T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,034 control chromosomes in the GnomAD database, including 24,603 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 (24603 hom., cov: 31)
• Consequence: TMTC1 NM_001193451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193451.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMTC1	NM_001193451.2	MANE Select	c.1676+8500T>C		intron	N/A	NP_001180380.1
	TMTC1	NM_001367875.2		c.1862+8500T>C		intron	N/A	NP_001354804.1
	TMTC1	NM_175861.3		c.1352+8500T>C		intron	N/A	NP_787057.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMTC1	ENST00000539277.6	TSL:1 MANE Select	c.1676+8500T>C		intron	N/A	ENSP00000442046.1
	TMTC1	ENST00000256062.9	TSL:1	c.1352+8500T>C		intron	N/A	ENSP00000256062.5
	TMTC1	ENST00000551659.6	TSL:5	c.1862+8500T>C		intron	N/A	ENSP00000448112.1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80855 AN: 151916 Hom.: 24605 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.532 AC: 80851 AN: 152034 Hom.: 24603 Cov.: 31 AF XY: 0.534 AC XY: 39672 AN XY: 74302

African (AFR) AF: 0.221 AC: 9162 AN: 41468

American (AMR) AF: 0.634 AC: 9690 AN: 15286

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

East Asian (EAS) AF: 0.553 AC: 2858 AN: 5166

South Asian (SAS) AF: 0.645 AC: 3106 AN: 4812

European-Finnish (FIN) AF: 0.619 AC: 6522 AN: 10544

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45257 AN: 67968

Other (OTH) AF: 0.559 AC: 1181 AN: 2114

Alfa AF: 0.591 Hom.: 6448

Bravo AF: 0.520

Asia WGS AF: 0.574 AC: 2001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.75
PhyloP100		0.097
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: rs299467; hg19: chr12-29701290;