Variant chr15-79313860-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_007364.4(TMED3):c.272G>A(p.Arg91Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00606 in 1,614,224 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0040 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0063 ( 37 hom. )

Consequence

TMED3
NM_007364.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0970

Variant links:

Genes affected

TMED3 (HGNC:28889): (transmembrane p24 trafficking protein 3) Predicted to be involved in Golgi organization; endoplasmic reticulum to Golgi vesicle-mediated transport; and intracellular protein transport. Located in Golgi apparatus; endoplasmic reticulum; and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]

TMED3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002995789).

BP6

Variant 15-79313860-G-A is Benign according to our data. Variant chr15-79313860-G-A is described in ClinVar as [Benign]. Clinvar id is 3033337.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMED3	NM_007364.4 linkuse as main transcript	c.272G>A	p.Arg91Gln	missense_variant	2/3	ENST00000299705.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMED3	ENST00000299705.10 linkuse as main transcript	c.272G>A	p.Arg91Gln	missense_variant	2/3	1	NM_007364.4	P1	Q9Y3Q3-1
TMED3	ENST00000424155.6 linkuse as main transcript	c.272G>A	p.Arg91Gln	missense_variant	2/3	3			Q9Y3Q3-2
TMED3	ENST00000536821.5 linkuse as main transcript	c.272G>A	p.Arg91Gln	missense_variant	2/3	2
TMED3	ENST00000543455.1 linkuse as main transcript	c.272G>A	p.Arg91Gln	missense_variant, NMD_transcript_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.00401

AC:

611

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00729

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00400

AC:

1006

AN:

251494

Hom.:

AF XY:

0.00401

AC XY:

545

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.00759

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00627

AC:

9173

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00613

AC XY:

4461

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00105

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00215

Gnomad4 NFE exome

AF:

0.00778

Gnomad4 OTH exome

AF:

0.00462

GnomAD4 genome

AF:

0.00401

AC:

611

AN:

152332

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

255

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00729

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00602

Hom.:

Bravo

AF:

0.00367

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.00722

AC:

ExAC

AF:

0.00446

AC:

542

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00491

EpiControl

AF:

0.00616

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TMED3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.7

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0069

T;.;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.36

N;N;N

REVEL

Benign

0.082

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.27

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.093

MVP

0.061

MPC

0.37

ClinPred

0.0047

GERP RS

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.033

gMVP

0.20

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

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