15-79313921-C-A

Variant names:

• chr15-79313921-C-A
• rs773718074
• NM_007364.4:c.333C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007364.4(TMED3):​c.333C>A​(p.His111Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H111H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMED3 NM_007364.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMED3	NM_007364.4	MANE Select	c.333C>A	p.His111Gln	missense	Exon 2 of 3	NP_031390.1	A0A140VKD1
	TMED3	NM_001330376.2		c.333C>A	p.His111Gln	missense	Exon 2 of 3	NP_001317305.1	Q9Y3Q3-2
	TMED3	NM_001301203.3		c.333C>A	p.His111Gln	missense	Exon 2 of 3	NP_001288132.1	F5H4M7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMED3	ENST00000299705.10	TSL:1 MANE Select	c.333C>A	p.His111Gln	missense	Exon 2 of 3	ENSP00000299705.5	Q9Y3Q3-1
	TMED3	ENST00000964020.1		c.333C>A	p.His111Gln	missense	Exon 2 of 3	ENSP00000634079.1
	TMED3	ENST00000424155.6	TSL:3	c.333C>A	p.His111Gln	missense	Exon 2 of 3	ENSP00000414983.2	Q9Y3Q3-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-7.7	D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.70
MutPred		0.41		Gain of sheet (P = 0.0827)
MVP		0.37
MPC		0.97
ClinPred		0.99	D
GERP RS		1.7
Varity_R		0.96
gMVP		0.57
Mutation Taster		=13/87	disease causing

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: rs773718074; hg19: chr15-79606263;