rs17578868

Variant names:

• chr13-100629321-A-G
• rs17578868
• NM_032813.5:c.1507-3171T>C

Variant summary

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

The NM_032813.5(TMTC4):​c.1507-3171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,080 control chromosomes in the GnomAD database, including 1,552 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 0.14 (1552 hom., cov: 31)
• Consequence: TMTC4 NM_032813.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 5 publications found

Genes affected

TMTC4 (HGNC:25904): (transmembrane O-mannosyltransferase targeting cadherins 4) This gene encodes a transmembrane protein that belongs to family of proteins containing an N-terminal transmembrane domain and a C-terminal tetratricopeptide repeat (TPR) domain. TPR domains mediate protein-protein interactions in various cellular processes, such as synaptic vesicle fusion, protein folding, and protein translocation. A pseudogene of this gene has been defined on chromosome 5. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.159 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032813.5. 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
	TMTC4	NM_032813.5	MANE Select	c.1507-3171T>C		intron	N/A	NP_116202.2
	TMTC4	NM_001350571.2		c.1681-3171T>C		intron	N/A	NP_001337500.1
	TMTC4	NM_001350574.2		c.1624-3171T>C		intron	N/A	NP_001337503.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMTC4	ENST00000342624.10	TSL:2 MANE Select	c.1507-3171T>C		intron	N/A	ENSP00000343871.5
	TMTC4	ENST00000376234.7	TSL:1	c.1450-3171T>C		intron	N/A	ENSP00000365408.3
	TMTC4	ENST00000462211.5	TSL:1	n.867-3171T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20767 AN: 151964 Hom.: 1552 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.137 AC: 20774 AN: 152080 Hom.: 1552 Cov.: 31 AF XY: 0.135 AC XY: 10045 AN XY: 74346

African (AFR) AF: 0.105 AC: 4364 AN: 41496

American (AMR) AF: 0.113 AC: 1728 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3468

East Asian (EAS) AF: 0.0271 AC: 140 AN: 5174

South Asian (SAS) AF: 0.143 AC: 686 AN: 4806

European-Finnish (FIN) AF: 0.152 AC: 1606 AN: 10580

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.161 AC: 10953 AN: 67962

Other (OTH) AF: 0.143 AC: 302 AN: 2116

Alfa AF: 0.153 Hom.: 3452

Bravo AF: 0.132

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.23
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs17578868; hg19: chr13-101281575;