chr14-75132452-G-A

Variant names:

• chr14-75132452-G-A
• rs13099
• NM_006827.6:c.*2433C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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]

ENSG00000259138 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMED10	NM_006827.6	c.*2433C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000303575.9	NP_006818.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMED10	ENST00000303575.9	c.*2433C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_006827.6	ENSP00000303145.4
ENSG00000259138	ENST00000556236.2	n.288-4320G>A		intron_variant	Intron 1 of 1	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.557 AC: 22078 AN: 39654

American (AMR) AF: 0.398 AC: 5712 AN: 14354

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1788 AN: 3462

East Asian (EAS) AF: 0.155 AC: 767 AN: 4942

South Asian (SAS) AF: 0.516 AC: 2429 AN: 4710

European-Finnish (FIN) AF: 0.506 AC: 4724 AN: 9336

Middle Eastern (MID) AF: 0.571 AC: 160 AN: 280

European-Non Finnish (NFE) AF: 0.510 AC: 34399 AN: 67484

Other (OTH) AF: 0.505 AC: 1034 AN: 2048

Alfa AF: 0.493 Hom.: 23360

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
PhyloP100		0.54
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: rs13099; hg19: chr14-75599155;