13-100624630-A-G

Variant names:

• chr13-100624630-A-G
• rs9554711
• NM_032813.5:c.1836+905T>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.1836+905T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,128 control chromosomes in the GnomAD database, including 8,690 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 0.33 (8690 hom., cov: 33)
• Consequence: TMTC4 NM_032813.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.806
• Publications: 2 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]

COX5BP6 (HGNC:2275): (cytochrome c oxidase subunit 5B pseudogene 6)

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 (EAS) allele frequency at 95% confidence interval = 0.569 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.1836+905T>C		intron	N/A	NP_116202.2
	TMTC4	NM_001350571.2		c.2010+905T>C		intron	N/A	NP_001337500.1
	TMTC4	NM_001350574.2		c.1953+905T>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.1836+905T>C		intron	N/A	ENSP00000343871.5
	TMTC4	ENST00000376234.7	TSL:1	c.1779+905T>C		intron	N/A	ENSP00000365408.3
	TMTC4	ENST00000328767.9	TSL:2	c.1446+905T>C		intron	N/A	ENSP00000365409.2

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50404 AN: 152010 Hom.: 8690 Cov.: 33

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.331 AC: 50423 AN: 152128 Hom.: 8690 Cov.: 33 AF XY: 0.340 AC XY: 25246 AN XY: 74358

African (AFR) AF: 0.344 AC: 14267 AN: 41518

American (AMR) AF: 0.253 AC: 3863 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1142 AN: 3472

East Asian (EAS) AF: 0.586 AC: 3024 AN: 5160

South Asian (SAS) AF: 0.374 AC: 1802 AN: 4818

European-Finnish (FIN) AF: 0.440 AC: 4648 AN: 10566

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20670 AN: 67980

Other (OTH) AF: 0.284 AC: 600 AN: 2116

Alfa AF: 0.322 Hom.: 1043

Bravo AF: 0.317

Asia WGS AF: 0.403 AC: 1403 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	11
DANN	Benign	0.74
PhyloP100		0.81
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: rs9554711; hg19: chr13-101276884;