Variant 16-69343604-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_144676.4(TMED6):c.526A>G(p.Met176Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

TMED6
NM_144676.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.78

Variant links:

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]

TMED6 links:

ENSG00000260371 (HGNC:):

ENSG00000260371 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29431233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMED6	NM_144676.4 link	c.526A>G	p.Met176Val	missense_variant	4/4	ENST00000288025.4	NP_653277.2	Q8WW62

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMED6	ENST00000288025.4 link	c.526A>G	p.Met176Val	missense_variant	4/4	1	NM_144676.4	ENSP00000288025.3	Q8WW62
ENSG00000260371	ENST00000563634.1 link	c.3-6892A>G		intron_variant		4		ENSP00000454500.1	H3BMQ9
ENSG00000259900	ENST00000564737.1 link	n.465+4184A>G		intron_variant		5		ENSP00000462747.1	J3KT08

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727222

show subpopulations

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:

0.0000216

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2023

The c.526A>G (p.M176V) alteration is located in exon 4 (coding exon 4) of the TMED6 gene. This alteration results from a A to G substitution at nucleotide position 526, causing the methionine (M) at amino acid position 176 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.80

M_CAP

Benign

0.019

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

2.9

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.4

REVEL

Benign

0.15

Sift

Benign

0.095

Sift4G

Uncertain

0.025

Polyphen

0.64

Vest4

0.35

MutPred

0.66

Loss of MoRF binding (P = 0.1078);

MVP

0.040

MPC

0.065

ClinPred

0.72

GERP RS

5.7

Varity_R

0.38

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over