Variant 1-93156385-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000370282.8(TMED5):c.386T>A(p.Met129Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,461,520 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M129T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

TMED5
ENST00000370282.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

Variant links:

Genes affected

TMED5 (HGNC:24251): (transmembrane p24 trafficking protein 5) Involved in Golgi ribbon formation. Located in cis-Golgi network; endoplasmic reticulum exit site; and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]

TMED5 links:

TMED5 (HGNC:):

TMED5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMED5	NM_016040.5 linkuse as main transcript	c.386T>A	p.Met129Lys	missense_variant	3/4	ENST00000370282.8	NP_057124.3	Q9Y3A6-1
TMED5	NM_001167830.2 linkuse as main transcript	c.386T>A	p.Met129Lys	missense_variant	3/5		NP_001161302.1	Q9Y3A6-2
TMED5	NM_001410825.1 linkuse as main transcript	c.*94T>A		3_prime_UTR_variant	4/4		NP_001397754.1
TMED5	NR_030761.2 linkuse as main transcript	n.628T>A		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMED5	ENST00000370282.8 linkuse as main transcript	c.386T>A	p.Met129Lys	missense_variant	3/4	1	NM_016040.5	ENSP00000359305.3		Q9Y3A6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251332

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461520

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.386T>A (p.M129K) alteration is located in exon 3 (coding exon 3) of the TMED5 gene. This alteration results from a T to A substitution at nucleotide position 386, causing the methionine (M) at amino acid position 129 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Benign

0.89

DEOGEN2

Benign

0.0016

T;.;T

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.54

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.83

N;N;N

REVEL

Uncertain

0.31

Sift

Benign

0.50

T;T;T

Sift4G

Benign

0.91

T;T;T

Polyphen

0.097

B;.;.

Vest4

0.72

MVP

0.42

MPC

0.49

ClinPred

0.43

GERP RS

4.5

Varity_R

0.71

gMVP

0.79

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