rs1114640

chr15-79344765-A-Gchr15-79344765-A-T

Variant summary

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

The NM_001330376.2(TMED3):c.417+30760A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 152,216 control chromosomes in the GnomAD database, including 55,972 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 0.86 (55972 hom., cov: 32)
• Consequence: TMED3 NM_001330376.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMED3	NM_001301203.3	c.417+30760A>G		intron_variant
TMED3	NM_001330376.2	c.417+30760A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMED3	ENST00000424155.6	c.417+30760A>G		intron_variant		3
TMED3	ENST00000536821.5	c.417+30760A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130145 AN: 152098 Hom.: 55950 Cov.: 32

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.852

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.855 AC: 130218 AN: 152216 Hom.: 55972 Cov.: 32 AF XY: 0.853 AC XY: 63459 AN XY: 74430

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.832

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.896

Gnomad4 NFE AF: 0.885

Gnomad4 OTH AF: 0.853

Alfa AF: 0.861 Hom.: 21201

Bravo AF: 0.849

Asia WGS AF: 0.714 AC: 2487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.9
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1114640; hg19: chr15-79637107;