15-79312440-A-G

Variant names:

• chr15-79312440-A-G
• rs11858942
• NM_007364.4:c.168+1023A>G

Variant summary

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

The NM_007364.4(TMED3):​c.168+1023A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,134 control chromosomes in the GnomAD database, including 7,604 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 0.30 (7604 hom., cov: 32)
• Consequence: TMED3 NM_007364.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331
• Publications: 9 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007364.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMED3	NM_007364.4	MANE Select	c.168+1023A>G		intron	N/A	NP_031390.1
	TMED3	NM_001330376.2		c.168+1023A>G		intron	N/A	NP_001317305.1
	TMED3	NM_001301203.3		c.168+1023A>G		intron	N/A	NP_001288132.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMED3	ENST00000299705.10	TSL:1 MANE Select	c.168+1023A>G		intron	N/A	ENSP00000299705.5
	TMED3	ENST00000424155.6	TSL:3	c.168+1023A>G		intron	N/A	ENSP00000414983.2
	TMED3	ENST00000536821.5	TSL:2	c.168+1023A>G		intron	N/A	ENSP00000446062.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45010 AN: 152016 Hom.: 7605 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.296 AC: 45011 AN: 152134 Hom.: 7604 Cov.: 32 AF XY: 0.294 AC XY: 21841 AN XY: 74362

African (AFR) AF: 0.132 AC: 5464 AN: 41542

American (AMR) AF: 0.305 AC: 4669 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1151 AN: 3468

East Asian (EAS) AF: 0.195 AC: 1007 AN: 5168

South Asian (SAS) AF: 0.364 AC: 1752 AN: 4808

European-Finnish (FIN) AF: 0.313 AC: 3306 AN: 10574

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26588 AN: 67972

Other (OTH) AF: 0.319 AC: 674 AN: 2112

Alfa AF: 0.342 Hom.: 16584

Bravo AF: 0.289

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.64
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11858942; hg19: chr15-79604782;