rs11858942

Positions:

• chr15-79312440-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMED3	NM_007364.4	c.168+1023A>G		intron_variant		ENST00000299705.10	NP_031390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMED3	ENST00000299705.10	c.168+1023A>G		intron_variant		1	NM_007364.4	ENSP00000299705	P1
TMED3	ENST00000424155.6	c.168+1023A>G		intron_variant		3		ENSP00000414983
TMED3	ENST00000536821.5	c.168+1023A>G		intron_variant		2		ENSP00000446062
TMED3	ENST00000543455.1	c.168+1023A>G		intron_variant, NMD_transcript_variant		2		ENSP00000440228

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

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.319

Alfa AF: 0.372 Hom.: 11083

Bravo AF: 0.289

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs11858942; hg19: chr15-79604782;