Variant chr15-79311418-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 4P and 6B. PVS1_StrongBP6_ModerateBS2

The NM_007364.4(TMED3):c.168+1G>A variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,604,818 control chromosomes in the GnomAD database, including 21 homozygotes. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 17 hom. )

Consequence

TMED3
NM_007364.4 splice_donor

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.09

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 -2 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.46636087 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

BP6

Variant 15-79311418-G-A is Benign according to our data. Variant chr15-79311418-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645626.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMED3	NM_007364.4 linkuse as main transcript	c.168+1G>A		splice_donor_variant		ENST00000299705.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
TMED3	ENST00000299705.10 linkuse as main transcript	c.168+1G>A	splice_donor_variant	1	NM_007364.4	P1	Q9Y3Q3-1
TMED3	ENST00000424155.6 linkuse as main transcript	c.168+1G>A	splice_donor_variant	3			Q9Y3Q3-2
TMED3	ENST00000536821.5 linkuse as main transcript	c.168+1G>A	splice_donor_variant	2
TMED3	ENST00000543455.1 linkuse as main transcript	c.168+1G>A	splice_donor_variant, NMD_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00373

AC:

567

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00980

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00509

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00319

AC:

740

AN:

231840

Hom.:

AF XY:

0.00304

AC XY:

385

AN XY:

126538

show subpopulations

Gnomad AFR exome

AF:

0.000421

Gnomad AMR exome

AF:

0.000952

Gnomad ASJ exome

AF:

0.00472

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000731

Gnomad FIN exome

AF:

0.00790

Gnomad NFE exome

AF:

0.00447

Gnomad OTH exome

AF:

0.00352

GnomAD4 exome

AF:

0.00369

AC:

5353

AN:

1452584

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

2676

AN XY:

721626

show subpopulations

Gnomad4 AFR exome

AF:

0.000332

Gnomad4 AMR exome

AF:

0.000972

Gnomad4 ASJ exome

AF:

0.00503

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000720

Gnomad4 FIN exome

AF:

0.00689

Gnomad4 NFE exome

AF:

0.00412

Gnomad4 OTH exome

AF:

0.00302

GnomAD4 genome

AF:

0.00372

AC:

567

AN:

152234

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

297

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00980

Gnomad4 NFE

AF:

0.00509

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00450

Hom.:

Bravo

AF:

0.00308

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000683

AC:

ESP6500EA

AF:

0.00443

AC:

ExAC

AF:

0.00286

AC:

346

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

TMED3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

1.2

Eigen_PC

Pathogenic

0.99

FATHMM_MKL

Pathogenic

0.97

MutationTaster

Benign

1.0

D;D;D

GERP RS

4.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.94

SpliceAI score (max)

1.0

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.72

Position offset: 45

DS_DL_spliceai

1.0

Position offset: -1

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