Variant 15-79322219-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_007364.4(TMED3):c.*5G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000295 in 1,609,998 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

TMED3
NM_007364.4 3_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.415

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 15-79322219-G-A is Benign according to our data. Variant chr15-79322219-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3054648.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
TMED3	NM_007364.4 linkuse as main transcript	c.*5G>A	3_prime_UTR_variant	3/3	ENST00000299705.10
TMED3	NM_001301203.3 linkuse as main transcript	c.417+8214G>A	intron_variant
TMED3	NM_001330376.2 linkuse as main transcript	c.417+8214G>A	intron_variant
TMED3	NR_125394.2 linkuse as main transcript	n.912G>A	non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMED3	ENST00000299705.10 linkuse as main transcript	c.*5G>A		3_prime_UTR_variant	3/3	1	NM_007364.4	P1	Q9Y3Q3-1

Frequencies

GnomAD3 genomes

AF:

0.00166

AC:

252

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00572

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000456

AC:

113

AN:

247822

Hom.:

AF XY:

0.000299

AC XY:

AN XY:

133688

show subpopulations

Gnomad AFR exome

AF:

0.00640

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000893

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000153

AC:

223

AN:

1457694

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

101

AN XY:

724636

show subpopulations

Gnomad4 AFR exome

AF:

0.00583

Gnomad4 AMR exome

AF:

0.000180

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000631

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.00165

AC:

252

AN:

152304

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

116

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00570

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000959

Hom.:

Bravo

AF:

0.00179

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TMED3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 11, 2020

This variant is classified as likely 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

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.7

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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