Genetic Variant TMED1:p.Gly25Glu (chr19-10836118-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006858.4(TMED1):c.74G>A(p.Gly25Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000369 in 1,573,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

TMED1
NM_006858.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.41

Publications

0 publications found

Variant links:

Genes affected

TMED1 (HGNC:17291): (transmembrane p24 trafficking protein 1) This gene belongs to the TMED (transmembrane emp24 domain-containing) protein family, which is involved in the vesicular trafficking of proteins. The protein encoded by this gene was identified by its interaction with interleukin 1 receptor-like 1 (IL1RL1) and may play a role in innate immunity. This protein lacks any similarity to other interleukin 1 ligands. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

TMED1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006858.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMED1	NM_006858.4	MANE Select	c.74G>A	p.Gly25Glu	missense	Exon 1 of 4	NP_006849.1	Q13445

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMED1	ENST00000214869.7	TSL:1 MANE Select	c.74G>A	p.Gly25Glu	missense	Exon 1 of 4	ENSP00000214869.1	Q13445
TMED1	ENST00000589638.1	TSL:5	c.74G>A	p.Gly25Glu	missense	Exon 1 of 4	ENSP00000467690.1	K7EQ63
TMED1	ENST00000591695.5	TSL:5	c.74G>A	p.Gly25Glu	missense	Exon 1 of 3	ENSP00000468294.1	K7ERK5

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000341

AC:

AN:

175718

AF XY:

0.0000313

show subpopulations

Gnomad AFR exome

AF:

0.000602

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000197

AC:

AN:

1421326

Hom.:

Cov.:

AF XY:

0.0000199

AC XY:

AN XY:

704048

show subpopulations

African (AFR)

AF:

0.000827

AC:

AN:

32654

American (AMR)

AF:

0.00

AC:

AN:

38418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25346

East Asian (EAS)

AF:

0.00

AC:

AN:

37492

South Asian (SAS)

AF:

0.00

AC:

AN:

81682

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092748

Other (OTH)

AF:

0.0000170

AC:

AN:

58820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000197

AC:

AN:

152380

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.000721

AC:

AN:

41596

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000201

Hom.:

Bravo

AF:

0.000227

ExAC

AF:

0.0000425

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.040

Eigen

Benign

-0.038

Eigen_PC

Benign

-0.070

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.77

M_CAP

Benign

0.0081

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

2.4

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.3

REVEL

Benign

0.18

Sift

Uncertain

0.027

Sift4G

Benign

1.0

Polyphen

1.0

Vest4

0.66

MVP

0.45

MPC

0.36

ClinPred

0.12

GERP RS

4.7

PromoterAI

0.086

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.16

gMVP

0.50

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.22

Position offset: -20

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over