rs7187579

chr16-69350956-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMED6	NM_144676.4	c.213+585G>A		intron_variant		ENST00000288025.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMED6	ENST00000288025.4	c.213+585G>A		intron_variant		1	NM_144676.4	P1

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

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.173

Alfa AF: 0.166 Hom.: 1119

Bravo AF: 0.152

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.95
Dann	Benign	0.57

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: rs7187579; hg19: chr16-69384859;