rs925114

Variant names:

• chr15-79413177-A-G
• rs925114
• XM_011521392.2:c.-431A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330376.2(TMED3):​c.*1673A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,088 control chromosomes in the GnomAD database, including 14,297 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 0.43 (14293 hom., cov: 32)
  • Exomes 𝑓: 0.75 (4 hom.)
• Consequence: TMED3 NM_001330376.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 2 publications found

Genes affected

MINAR1 (HGNC:29172): (membrane integral NOTCH2 associated receptor 1) Involved in several processes, including negative regulation of TOR signaling; negative regulation of angiogenesis; and negative regulation of protein ubiquitination. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330376.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMED3	NM_001330376.2		c.*1673A>G		3_prime_UTR	Exon 3 of 3	NP_001317305.1	Q9Y3Q3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMED3	ENST00000424155.6	TSL:3	c.*1673A>G		3_prime_UTR	Exon 3 of 3	ENSP00000414983.2	Q9Y3Q3-2

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64912 AN: 151958 Hom.: 14291 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.750 AC: 9 AN: 12 Hom.: 4 Cov.: 0 AF XY: 0.700 AC XY: 7 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.700 AC: 7 AN: 10

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.427 AC: 64918 AN: 152076 Hom.: 14293 Cov.: 32 AF XY: 0.421 AC XY: 31276 AN XY: 74334

African (AFR) AF: 0.338 AC: 14014 AN: 41460

American (AMR) AF: 0.357 AC: 5457 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1643 AN: 3472

East Asian (EAS) AF: 0.352 AC: 1817 AN: 5168

South Asian (SAS) AF: 0.519 AC: 2503 AN: 4820

European-Finnish (FIN) AF: 0.392 AC: 4146 AN: 10578

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33790 AN: 67968

Other (OTH) AF: 0.445 AC: 939 AN: 2110

Alfa AF: 0.465 Hom.: 24567

Bravo AF: 0.417

Asia WGS AF: 0.410 AC: 1427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.5
DANN	Benign	0.81
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs925114; hg19: chr15-79705519;