Genetic Variant CTAGE6:p.Glu473Val (chr7-143756241-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178561.5(CTAGE6):c.1418A>T(p.Glu473Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000687 in 145,614 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 23)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CTAGE6
NM_178561.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTAGE6	NM_178561.5 link	c.1418A>T	p.Glu473Val	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.1418A>T	p.Glu473Val	missense_variant	Exon 1 of 1	6	NM_178561.5	ENSP00000474388.1		Q86UF2
ENSG00000291149	ENST00000700950.1 link	n.178+12857A>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00000687

AC:

AN:

145614

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:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000762

AC:

AN:

1443256

Hom.:

Cov.:

AF XY:

0.00000419

AC XY:

AN XY:

716644

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:

0.00000999

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000687

AC:

AN:

145614

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70996

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:

0.0000152

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000169

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1418A>T (p.E473V) alteration is located in exon 1 (coding exon 1) of the CTAGE6 gene. This alteration results from a A to T substitution at nucleotide position 1418, causing the glutamic acid (E) at amino acid position 473 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

Pathogenic

0.60

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Uncertain

0.43

FATHMM_MKL

Benign

0.19

M_CAP

Benign

0.0052

MetaRNN

Uncertain

0.48

MutationAssessor

Pathogenic

3.6

PrimateAI

Uncertain

0.68

Sift4G

Uncertain

0.018

Polyphen

1.0

Vest4

0.42

MVP

0.62

GERP RS

0.11

Varity_R

0.15

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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