dbSNP rs9302288: TMED3:c.418-28441T>C (chr15-79382959-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001330376.2(TMED3):c.418-28441T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,534,894 control chromosomes in the GnomAD database, including 14,348 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2371 hom., cov: 32)

Exomes 𝑓: 0.13 ( 11977 hom. )

Consequence

TMED3
NM_001330376.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

Publications

6 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMED3	NM_001330376.2 link	c.418-28441T>C		intron_variant	Intron 2 of 2		NP_001317305.1	Q9Y3Q3-2
TMED3	NM_001301203.3 link	c.418-9T>C		intron_variant	Intron 2 of 2		NP_001288132.1	F5H4M7B4E277

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMED3	ENST00000424155.6 link	c.418-28441T>C		intron_variant	Intron 2 of 2	3		ENSP00000414983.2		Q9Y3Q3-2
TMED3	ENST00000536821.5 link	c.418-9T>C		intron_variant	Intron 2 of 2	2		ENSP00000446062.1		F5H4M7

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25262

AN:

152068

Hom.:

2366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.160

GnomAD2 exomes

AF:

0.150

AC:

19168

AN:

128066

AF XY:

0.142

show subpopulations

Gnomad AFR exome

AF:

0.240

Gnomad AMR exome

AF:

0.209

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.181

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.127

AC:

175925

AN:

1382708

Hom.:

11977

Cov.:

AF XY:

0.126

AC XY:

85695

AN XY:

682328

show subpopulations

African (AFR)

AF:

0.249

AC:

7839

AN:

31534

American (AMR)

AF:

0.198

AC:

7068

AN:

35690

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

3507

AN:

25176

East Asian (EAS)

AF:

0.194

AC:

6940

AN:

35730

South Asian (SAS)

AF:

0.0951

AC:

7536

AN:

79220

European-Finnish (FIN)

AF:

0.178

AC:

5964

AN:

33464

Middle Eastern (MID)

AF:

0.155

AC:

884

AN:

5686

European-Non Finnish (NFE)

AF:

0.119

AC:

128161

AN:

1078348

Other (OTH)

AF:

0.139

AC:

8026

AN:

57860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

7414

14827

22241

29654

37068

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4862

9724

14586

19448

24310

<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:

0.166

AC:

25303

AN:

152186

Hom.:

2371

Cov.:

AF XY:

0.169

AC XY:

12539

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.244

AC:

10135

AN:

41500

American (AMR)

AF:

0.167

AC:

2561

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

476

AN:

3472

East Asian (EAS)

AF:

0.197

AC:

1020

AN:

5176

South Asian (SAS)

AF:

0.105

AC:

506

AN:

4826

European-Finnish (FIN)

AF:

0.191

AC:

2028

AN:

10592

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.118

AC:

8038

AN:

68006

Other (OTH)

AF:

0.163

AC:

344

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1092

2184

3276

4368

5460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<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:

0.143

Hom.:

333

Bravo

AF:

0.175

Asia WGS

AF:

0.168

AC:

585

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.4

(source)

DANN

Benign

0.41

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over