chr5-177592261-C-G

Variant names:

• chr5-177592261-C-G
• rs57960711
• NM_017510.6:c.47C>G

Variant summary

Our verdict is Benign. The variant received -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. 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. 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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMED9	NM_017510.6	c.47C>G	p.Thr16Ser	missense_variant	Exon 1 of 5	ENST00000332598.7	NP_059980.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMED9	ENST00000332598.7	c.47C>G	p.Thr16Ser	missense_variant	Exon 1 of 5	1	NM_017510.6	ENSP00000330945.6
TMED9	ENST00000505521.1	n.45C>G		non_coding_transcript_exon_variant	Exon 1 of 2	2
TMED9	ENST00000507723.1	n.-11C>G		upstream_gene_variant		2
TMED9	ENST00000513799.5	n.-227C>G		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

GnomAD2 exomes AF: 0.0271 AC: 6526 AN: 240502 AF XY: 0.0266

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 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

African (AFR) AF: 0.0524 AC: 1750 AN: 33426

American (AMR) AF: 0.0269 AC: 1195 AN: 44490

Ashkenazi Jewish (ASJ) AF: 0.0224 AC: 583 AN: 26072

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39574

South Asian (SAS) AF: 0.00148 AC: 127 AN: 85794

European-Finnish (FIN) AF: 0.0281 AC: 1489 AN: 52964

Middle Eastern (MID) AF: 0.0123 AC: 69 AN: 5628

European-Non Finnish (NFE) AF: 0.0415 AC: 46115 AN: 1110950

Other (OTH) AF: 0.0337 AC: 2030 AN: 60214

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

African (AFR) AF: 0.0503 AC: 2093 AN: 41590

American (AMR) AF: 0.0318 AC: 487 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4832

European-Finnish (FIN) AF: 0.0246 AC: 261 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0390 AC: 2654 AN: 68020

Other (OTH) AF: 0.0416 AC: 88 AN: 2116

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
PhyloP100		-0.0070
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
PromoterAI		0.26	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.17
Mutation Taster		=98/2	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: rs57960711; hg19: chr5-177019262; COSMIC: COSV107406806;