rs13099

chr14-75132452-G-Achr14-75132452-G-C

Variant summary

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

The NM_006827.6(TMED10):c.*2433C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 147,168 control chromosomes in the GnomAD database, including 18,895 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 0.50 (18895 hom., cov: 24)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMED10 NM_006827.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMED10	NM_006827.6	c.*2433C>T		3_prime_UTR_variant	5/5	ENST00000303575.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMED10	ENST00000303575.9	c.*2433C>T		3_prime_UTR_variant	5/5	1	NM_006827.6	P1
	ENST00000556236.1	n.209-4320G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.500 AC: 73518 AN: 147056 Hom.: 18874 Cov.: 24

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.581

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.499

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 SAS exome AF: 0.00

GnomAD4 genome AF: 0.500 AC: 73568 AN: 147168 Hom.: 18895 Cov.: 24 AF XY: 0.497 AC XY: 35404 AN XY: 71188

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.505

Alfa AF: 0.489 Hom.: 17411

Bravo AF: 0.488

Asia WGS AF: 0.392 AC: 1364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	9.5
Dann	Benign	0.83

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: rs13099; hg19: chr14-75599155;