rs868343566

Variant names:

• chr15-79313812-A-G
• rs868343566
• NM_007364.4:c.224A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-79313812-A-G
• chr15-79313812-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007364.4(TMED3):​c.224A>G​(p.Asn75Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N75I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: TMED3 NM_007364.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079358935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMED3	NM_007364.4	c.224A>G	p.Asn75Ser	missense_variant	Exon 2 of 3	ENST00000299705.10	NP_031390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMED3	ENST00000299705.10	c.224A>G	p.Asn75Ser	missense_variant	Exon 2 of 3	1	NM_007364.4	ENSP00000299705.5
TMED3	ENST00000424155.6	c.224A>G	p.Asn75Ser	missense_variant	Exon 2 of 3	3		ENSP00000414983.2
TMED3	ENST00000536821.5	c.224A>G	p.Asn75Ser	missense_variant	Exon 2 of 3	2		ENSP00000446062.1
TMED3	ENST00000543455.1	n.224A>G		non_coding_transcript_exon_variant	Exon 2 of 4	2		ENSP00000440228.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000144

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Benign	0.84
DEOGEN2	Benign	0.011	T;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.079	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.87	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.51	T;T;T
Sift4G	Benign	0.65	T;T;T
Polyphen		0.030	B;.;.
Vest4		0.061
MutPred		0.38		Gain of disorder (P = 0.0668);Gain of disorder (P = 0.0668);Gain of disorder (P = 0.0668);
MVP		0.13
MPC		0.28
ClinPred		0.19	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.32

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: rs868343566; hg19: chr15-79606154;