rs17578868

chr13-100629321-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMTC4	NM_032813.5	c.1507-3171T>C		intron_variant		ENST00000342624.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMTC4	ENST00000342624.10	c.1507-3171T>C		intron_variant		2	NM_032813.5

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

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.0271

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.143

Alfa AF: 0.156 Hom.: 2569

Bravo AF: 0.132

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.0
Dann	Benign	0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs17578868; hg19: chr13-101281575;