Genetic Variant CTAGE6:p.Ala484Val (chr7-143756208-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_178561.5(CTAGE6):c.1451C>T(p.Ala484Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A484P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., cov: 22)

Exomes 𝑓: 0.000032 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

CTAGE6
NM_178561.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

Variant links:

Genes affected

CTAGE6 (HGNC:28644): (CTAGE family member 6) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport; protein secretion; and vesicle cargo loading. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum exit site and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

CTAGE6 links:

ENSG00000291149 (HGNC:):

ENSG00000291149 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20757481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTAGE6	NM_178561.5 link	c.1451C>T	p.Ala484Val	missense_variant	Exon 1 of 1	ENST00000470691.2	NP_848656.2	Q86UF2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTAGE6	ENST00000470691.2 link	c.1451C>T	p.Ala484Val	missense_variant	Exon 1 of 1	6	NM_178561.5	ENSP00000474388.1		Q86UF2
ENSG00000291149	ENST00000700950.1 link	n.178+12890C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

143504

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000703

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:

0.000108

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000292

AC:

AN:

171028

Hom.:

AF XY:

0.0000322

AC XY:

AN XY:

93038

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000740

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000507

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000324

AC:

AN:

1419690

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

703608

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000394

Gnomad4 OTH exome

AF:

0.0000342

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000627

AC:

AN:

143504

Hom.:

Cov.:

AF XY:

0.0000859

AC XY:

AN XY:

69818

show subpopulations

Gnomad4 AFR

AF:

0.0000257

Gnomad4 AMR

AF:

0.0000703

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000108

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000973

Hom.:

ExAC

AF:

0.0000436

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1451C>T (p.A484V) alteration is located in exon 1 (coding exon 1) of the CTAGE6 gene. This alteration results from a C to T substitution at nucleotide position 1451, causing the alanine (A) at amino acid position 484 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

0.17

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.27

FATHMM_MKL

Benign

0.12

M_CAP

Benign

0.0044

MetaRNN

Benign

0.21

MutationAssessor

Uncertain

2.8

PrimateAI

Uncertain

0.57

Sift4G

Benign

0.21

Polyphen

0.97

Vest4

0.19

MVP

0.54

GERP RS

0.11

Varity_R

0.073

gMVP

0.27

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

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