14-75159339-A-C

Variant names:

• chr14-75159339-A-C
• rs910316
• NM_006827.6:c.226-7196T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 40 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006827.6. 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
	TMED10	NM_006827.6	MANE Select	c.226-7196T>G		intron	N/A	NP_006818.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMED10	ENST00000303575.9	TSL:1 MANE Select	c.226-7196T>G		intron	N/A	ENSP00000303145.4
	TMED10	ENST00000555873.1	TSL:1	n.226-7196T>G		intron	N/A	ENSP00000450726.1
	TMED10	ENST00000555085.1	TSL:2	n.259-7196T>G		intron	N/A

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

African (AFR) AF: 0.315 AC: 13082 AN: 41468

American (AMR) AF: 0.589 AC: 8995 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1663 AN: 3468

East Asian (EAS) AF: 0.836 AC: 4326 AN: 5174

South Asian (SAS) AF: 0.437 AC: 2108 AN: 4820

European-Finnish (FIN) AF: 0.492 AC: 5192 AN: 10562

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32786 AN: 67986

Other (OTH) AF: 0.462 AC: 976 AN: 2112

Alfa AF: 0.480 Hom.: 44387

Bravo AF: 0.464

Asia WGS AF: 0.572 AC: 1991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		2.0
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: rs910316; hg19: chr14-75626042;