Genetic Variant CTAGE6:p.Ala524Thr (chr7-143756089-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_178561.5(CTAGE6):c.1570G>A(p.Ala524Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A524S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 9)

Exomes 𝑓: 0.000023 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CTAGE6
NM_178561.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.965

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042453647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTAGE6	NM_178561.5 link	c.1570G>A	p.Ala524Thr	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.1570G>A	p.Ala524Thr	missense_variant	Exon 1 of 1	6	NM_178561.5	ENSP00000474388.1		Q86UF2
ENSG00000291149	ENST00000700950.1 link	n.178+13009G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

77340

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000303

AC:

AN:

66094

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

33612

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000297

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000231

AC:

AN:

1039182

Hom.:

Cov.:

AF XY:

0.0000233

AC XY:

AN XY:

515700

show subpopulations

Gnomad4 AFR exome

AF:

0.0000418

Gnomad4 AMR exome

AF:

0.0000957

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000198

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000749

Gnomad4 OTH exome

AF:

0.0000890

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

77340

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35034

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.4

DANN

Benign

0.59

DEOGEN2

Benign

0.055

FATHMM_MKL

Benign

0.013

M_CAP

Benign

0.0097

MetaRNN

Benign

0.042

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.51

Sift4G

Benign

0.19

Polyphen

0.0020

Vest4

0.038

MVP

0.13

GERP RS

-0.22

Varity_R

0.039

gMVP

0.37

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over