rs57960711

Positions:

• chr5-177592261-C-G

Variant summary

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

The NM_017510.6(TMED9):​c.47C>G​(p.Thr16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 1,611,446 control chromosomes in the GnomAD database, including 1,266 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T16A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.037 (117 hom., cov: 33)
  • Exomes 𝑓: 0.037 (1149 hom.)
• Consequence: TMED9 NM_017510.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

Genes affected

TMED9 (HGNC:24878): (transmembrane p24 trafficking protein 9) This gene is a member of a family of genes encoding transport proteins located in the endoplasmic reticulum and the Golgi. A similar gene in mouse is the target of microRNA miR-296, which is part of an imprinted cluster. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020644963).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMED9	NM_017510.6	c.47C>G	p.Thr16Ser	missense_variant	1/5	ENST00000332598.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMED9	ENST00000332598.7	c.47C>G	p.Thr16Ser	missense_variant	1/5	1	NM_017510.6	P1
TMED9	ENST00000505521.1	n.45C>G		non_coding_transcript_exon_variant	1/2	2
TMED9	ENST00000507723.1			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0372 AC: 5655 AN: 152220 Hom.: 117 Cov.: 33

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0319

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0420

GnomAD3 exomes AF: 0.0271 AC: 6526 AN: 240502 Hom.: 137 AF XY: 0.0266 AC XY: 3497 AN XY: 131462

Gnomad AFR exome AF: 0.0469

Gnomad AMR exome AF: 0.0254

Gnomad ASJ exome AF: 0.0222

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00120

Gnomad FIN exome AF: 0.0275

Gnomad NFE exome AF: 0.0368

Gnomad OTH exome AF: 0.0329

GnomAD4 exome AF: 0.0366 AC: 53359 AN: 1459112 Hom.: 1149 Cov.: 32 AF XY: 0.0355 AC XY: 25770 AN XY: 725630

Gnomad4 AFR exome AF: 0.0524

Gnomad4 AMR exome AF: 0.0269

Gnomad4 ASJ exome AF: 0.0224

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00148

Gnomad4 FIN exome AF: 0.0281

Gnomad4 NFE exome AF: 0.0415

Gnomad4 OTH exome AF: 0.0337

GnomAD4 genome AF: 0.0372 AC: 5664 AN: 152334 Hom.: 117 Cov.: 33 AF XY: 0.0361 AC XY: 2691 AN XY: 74494

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.0318

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0246

Gnomad4 NFE AF: 0.0390

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0360 Hom.: 78

Bravo AF: 0.0404

TwinsUK AF: 0.0423 AC: 157

ALSPAC AF: 0.0423 AC: 163

ESP6500AA AF: 0.0445 AC: 195

ESP6500EA AF: 0.0390 AC: 335

ExAC AF: 0.0263 AC: 3176

Asia WGS AF: 0.00346 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.55
DANN	Benign	0.32
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.044
Sift	Benign	0.54	T
Sift4G	Benign	0.80	T
Polyphen		0.0	B
Vest4		0.050
MutPred		0.095		Gain of glycosylation at T16 (P = 0.0213);
MPC		0.36
ClinPred		0.0035	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.17

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: rs57960711; hg19: chr5-177019262;