rs9302288

Positions:

• chr15-79382959-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001301203.3(TMED3):​c.418-9T>C variant causes a splice polypyrimidine tract, 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_001301203.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TMED3	NM_001301203.3	c.418-9T>C		splice_polypyrimidine_tract_variant, intron_variant			NP_001288132.1
TMED3	NM_001330376.2	c.418-28441T>C		intron_variant			NP_001317305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMED3	ENST00000424155.6	c.418-28441T>C		intron_variant		3		ENSP00000414983
TMED3	ENST00000536821.5	c.418-9T>C		splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000446062

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25262 AN: 152068 Hom.: 2366 Cov.: 32

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

GnomAD3 exomes AF: 0.150 AC: 19168 AN: 128066 Hom.: 1625 AF XY: 0.142 AC XY: 9956 AN XY: 70130

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 SAS exome AF: 0.0981

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.: 31 AF XY: 0.126 AC XY: 85695 AN XY: 682328

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.194

Gnomad4 SAS exome AF: 0.0951

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.166 AC: 25303 AN: 152186 Hom.: 2371 Cov.: 32 AF XY: 0.169 AC XY: 12539 AN XY: 74398

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.163

Alfa AF: 0.141 Hom.: 310

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
DANN	Benign	0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9302288; hg19: chr15-79675301; COSMIC: COSV69695253;