Variant 14-75135034-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006827.6(TMED10):c.539-28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,611,808 control chromosomes in the GnomAD database, including 194,617 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.43 ( 15964 hom., cov: 32)

Exomes 𝑓: 0.49 ( 178653 hom. )

Consequence

TMED10
NM_006827.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.343

Variant links:

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 links:

ENSG00000259138 (HGNC:):

ENSG00000259138 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 14-75135034-A-G is Benign according to our data. Variant chr14-75135034-A-G is described in ClinVar as [Benign]. Clinvar id is 1253710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
TMED10	NM_006827.6 link	c.539-28T>C		intron_variant	Intron 4 of 4	ENST00000303575.9	NP_006818.3	P49755A0A024R6I3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMED10	ENST00000303575.9 link	c.539-28T>C		intron_variant	Intron 4 of 4	1	NM_006827.6	ENSP00000303145.4		P49755

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65830

AN:

151922

Hom.:

15955

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.580

Gnomad ASJ

AF:

0.464

Gnomad EAS

AF:

0.836

Gnomad SAS

AF:

0.438

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.482

Gnomad OTH

AF:

0.450

GnomAD3 exomes

AF:

0.521

AC:

130499

AN:

250586

Hom.:

36709

AF XY:

0.512

AC XY:

69435

AN XY:

135558

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.723

Gnomad ASJ exome

AF:

0.465

Gnomad EAS exome

AF:

0.832

Gnomad SAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.486

Gnomad NFE exome

AF:

0.484

Gnomad OTH exome

AF:

0.496

GnomAD4 exome

AF:

0.487

AC:

710561

AN:

1459768

Hom.:

178653

Cov.:

AF XY:

0.485

AC XY:

352498

AN XY:

726198

show subpopulations

Gnomad4 AFR exome

AF:

0.218

Gnomad4 AMR exome

AF:

0.706

Gnomad4 ASJ exome

AF:

0.461

Gnomad4 EAS exome

AF:

0.828

Gnomad4 SAS exome

AF:

0.444

Gnomad4 FIN exome

AF:

0.484

Gnomad4 NFE exome

AF:

0.478

Gnomad4 OTH exome

AF:

0.483

GnomAD4 genome

AF:

0.433

AC:

65862

AN:

152040

Hom.:

15964

Cov.:

AF XY:

0.438

AC XY:

32547

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.581

Gnomad4 ASJ

AF:

0.464

Gnomad4 EAS

AF:

0.836

Gnomad4 SAS

AF:

0.438

Gnomad4 FIN

AF:

0.491

Gnomad4 NFE

AF:

0.482

Gnomad4 OTH

AF:

0.444

Alfa

AF:

0.393

Hom.:

2507

Bravo

AF:

0.436

Asia WGS

AF:

0.568

AC:

1974

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 26, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28233271) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.2

DANN

Benign

0.53

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over