rs7187579

Variant names:

• chr16-69350956-C-T
• rs7187579
• NM_144676.4:c.213+585G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144676.4(TMED6):​c.213+585G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,094 control chromosomes in the GnomAD database, including 1,934 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 0.15 (1934 hom., cov: 31)
• Consequence: TMED6 NM_144676.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 9 publications found

Genes affected

TMED6 (HGNC:28331): (transmembrane p24 trafficking protein 6) Predicted to be involved in Golgi organization; endoplasmic reticulum to Golgi vesicle-mediated transport; and intracellular protein transport. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in several cellular components, including COPII-coated ER to Golgi transport vesicle; Golgi apparatus; and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000260371 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144676.4. 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
	TMED6	NM_144676.4	MANE Select	c.213+585G>A		intron	N/A	NP_653277.2	Q8WW62

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMED6	ENST00000288025.4	TSL:1 MANE Select	c.213+585G>A		intron	N/A	ENSP00000288025.3	Q8WW62
	ENSG00000260371	ENST00000563634.1	TSL:4	c.2+5253G>A		intron	N/A	ENSP00000454500.1	H3BMQ9
	ENSG00000259900	ENST00000564737.1	TSL:5	n.189+585G>A		intron	N/A	ENSP00000462747.1	J3KT08

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23283 AN: 151976 Hom.: 1932 Cov.: 31

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.153 AC: 23301 AN: 152094 Hom.: 1934 Cov.: 31 AF XY: 0.150 AC XY: 11173 AN XY: 74346

African (AFR) AF: 0.142 AC: 5907 AN: 41476

American (AMR) AF: 0.129 AC: 1977 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 632 AN: 3470

East Asian (EAS) AF: 0.0214 AC: 111 AN: 5186

South Asian (SAS) AF: 0.121 AC: 583 AN: 4824

European-Finnish (FIN) AF: 0.130 AC: 1369 AN: 10556

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12200 AN: 67994

Other (OTH) AF: 0.173 AC: 364 AN: 2110

Alfa AF: 0.167 Hom.: 1251

Bravo AF: 0.152

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.95
DANN	Benign	0.57
PhyloP100		-0.49
Mutation Taster		=100/0	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: rs7187579; hg19: chr16-69384859;