Variant chr16-69351689-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000288025.4(TMED6):c.65A>C(p.Gln22Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TMED6
ENST00000288025.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.716

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07332957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMED6	NM_144676.4 linkuse as main transcript	c.65A>C	p.Gln22Pro	missense_variant	1/4	ENST00000288025.4	NP_653277.2	Q8WW62

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMED6	ENST00000288025.4 linkuse as main transcript	c.65A>C	p.Gln22Pro	missense_variant	1/4	1	NM_144676.4	ENSP00000288025.3	Q8WW62
ENSG00000260371	ENST00000563634.1 linkuse as main transcript	c.2+4520A>C		intron_variant		4		ENSP00000454500.1	H3BMQ9
ENSG00000259900	ENST00000564737.1 linkuse as main transcript	n.41A>C		non_coding_transcript_exon_variant	1/5	5		ENSP00000462747.1	J3KT08
ENSG00000259900	ENST00000570293.5 linkuse as main transcript	n.41A>C		non_coding_transcript_exon_variant	1/4	2		ENSP00000464417.1	J3QRW8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727176

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 02, 2024

The c.65A>C (p.Q22P) alteration is located in exon 1 (coding exon 1) of the TMED6 gene. This alteration results from a A to C substitution at nucleotide position 65, causing the glutamine (Q) at amino acid position 22 to be replaced by a proline (P). 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

0.071

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.60

M_CAP

Benign

0.0063

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.90

PrimateAI

Benign

0.38

PROVEAN

Benign

0.010

REVEL

Benign

0.22

Sift

Benign

0.31

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.23

MutPred

0.17

Gain of glycosylation at Q22 (P = 0.0198);

MVP

0.067

MPC

0.052

ClinPred

0.45

GERP RS

3.6

Varity_R

0.18

gMVP

0.26

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over