NM_001193451.2:c.1676+7605T>C

Variant names:

• chr12-29549252-A-G
• rs299470
• NM_001193451.2:c.1676+7605T>C

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+7605T>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 151,380 control chromosomes in the GnomAD database, including 24,670 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 (24670 hom., cov: 30)
• Consequence: TMTC1 NM_001193451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353
• 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.662 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMTC1	NM_001193451.2	MANE Select	c.1676+7605T>C		intron	N/A	NP_001180380.1	Q8IUR5-5
	TMTC1	NM_001367875.2		c.1862+7605T>C		intron	N/A	NP_001354804.1	F8VTQ9
	TMTC1	NM_175861.3		c.1352+7605T>C		intron	N/A	NP_787057.2	Q8IUR5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMTC1	ENST00000539277.6	TSL:1 MANE Select	c.1676+7605T>C		intron	N/A	ENSP00000442046.1	Q8IUR5-5
	TMTC1	ENST00000256062.9	TSL:1	c.1352+7605T>C		intron	N/A	ENSP00000256062.5	Q8IUR5-1
	TMTC1	ENST00000904147.1		c.1928+7605T>C		intron	N/A	ENSP00000574206.1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 80762 AN: 151260 Hom.: 24672 Cov.: 30

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.667

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: 80758 AN: 151380 Hom.: 24670 Cov.: 30 AF XY: 0.537 AC XY: 39659 AN XY: 73914

African (AFR) AF: 0.221 AC: 9135 AN: 41338

American (AMR) AF: 0.634 AC: 9592 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2307 AN: 3464

East Asian (EAS) AF: 0.554 AC: 2858 AN: 5156

South Asian (SAS) AF: 0.645 AC: 3107 AN: 4816

European-Finnish (FIN) AF: 0.634 AC: 6543 AN: 10324

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45283 AN: 67848

Other (OTH) AF: 0.557 AC: 1169 AN: 2098

Alfa AF: 0.582 Hom.: 4324

Bravo AF: 0.521

Asia WGS AF: 0.575 AC: 2000 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.8
DANN	Benign	0.91
PhyloP100		0.35
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: rs299470; hg19: chr12-29702185;