13-100624630-A-G

Variant names:

• chr13-100624630-A-G
• rs9554711
• NM_032813.5:c.1836+905T>C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMTC4	NM_032813.5	c.1836+905T>C		intron_variant	Intron 15 of 18	ENST00000342624.10	NP_116202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMTC4	ENST00000342624.10	c.1836+905T>C		intron_variant	Intron 15 of 18	2	NM_032813.5	ENSP00000343871.5
TMTC4	ENST00000376234.7	c.1779+905T>C		intron_variant	Intron 14 of 17	1		ENSP00000365408.3
TMTC4	ENST00000328767.9	c.1446+905T>C		intron_variant	Intron 12 of 15	2		ENSP00000365409.2
COX5BP6	ENST00000454311.1	n.-201T>C		upstream_gene_variant		6

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

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.284

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs9554711; hg19: chr13-101276884;