Genetic Variant TMED1:p.Ser84Gly (chr19-10835287-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006858.4(TMED1):c.250A>G(p.Ser84Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMED1
NM_006858.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28548884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMED1	NM_006858.4 link	c.250A>G	p.Ser84Gly	missense_variant	Exon 2 of 4	ENST00000214869.7	NP_006849.1	Q13445
TMED1	XM_006722631.4 link	c.136A>G	p.Ser46Gly	missense_variant	Exon 2 of 4		XP_006722694.1
TMED1	NR_104015.2 link	n.205A>G		non_coding_transcript_exon_variant	Exon 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMED1	ENST00000214869.7 link	c.250A>G	p.Ser84Gly	missense_variant	Exon 2 of 4	1	NM_006858.4	ENSP00000214869.1		Q13445

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251360

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461742

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.250A>G (p.S84G) alteration is located in exon 2 (coding exon 2) of the TMED1 gene. This alteration results from a A to G substitution at nucleotide position 250, causing the serine (S) at amino acid position 84 to be replaced by a glycine (G). 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

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.8

M;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.8

D;.;.

REVEL

Benign

0.18

Sift

Benign

0.34

T;.;.

Sift4G

Benign

0.16

T;T;.

Polyphen

0.74

P;.;.

Vest4

0.34

MutPred

0.38

Loss of phosphorylation at S84 (P = 0.0787);Loss of phosphorylation at S84 (P = 0.0787);Loss of phosphorylation at S84 (P = 0.0787);

MVP

0.42

MPC

0.36

ClinPred

0.55

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.32

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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