rs910316

Positions:

• chr14-75159339-A-C
• chr14-75159339-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006827.6(TMED10):​c.226-7196T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,062 control chromosomes in the GnomAD database, including 17,051 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 0.46 (17051 hom., cov: 32)
• Consequence: TMED10 NM_006827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

Genes affected

TMED10 (HGNC:16998): (transmembrane p24 trafficking protein 10) This gene is a member of the EMP24/GP25L/p24 family and encodes a protein with a GOLD domain. This type I membrane protein is localized to the plasma membrane and golgi cisternae and is involved in vesicular protein trafficking. The protein is also a member of a heteromeric secretase complex and regulates the complex's gamma-secretase activity without affecting its epsilon-secretase activity. Mutations in this gene have been associated with early-onset familial Alzheimer's disease. This gene has a pseudogene on chromosome 8. [provided by RefSeq, Jul 2008]

TMED10 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMED10	NM_006827.6	c.226-7196T>G		intron_variant		ENST00000303575.9	NP_006818.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMED10	ENST00000303575.9	c.226-7196T>G		intron_variant		1	NM_006827.6	ENSP00000303145.4
TMED10	ENST00000555873.1	n.226-7196T>G		intron_variant		1		ENSP00000450726.1
TMED10	ENST00000555085.1	n.259-7196T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69608 AN: 151944 Hom.: 17033 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.458 AC: 69666 AN: 152062 Hom.: 17051 Cov.: 32 AF XY: 0.462 AC XY: 34333 AN XY: 74328

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.836

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.462

Alfa AF: 0.487 Hom.: 28918

Bravo AF: 0.464

Asia WGS AF: 0.572 AC: 1991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.66

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: rs910316; hg19: chr14-75626042;