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

Variant summary

Our verdict is Likely benign. The variant received -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

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178561.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTAGE6	NM_178561.5	MANE Select	c.1570G>A	p.Ala524Thr	missense	Exon 1 of 1	NP_848656.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTAGE6	ENST00000470691.2	TSL:6 MANE Select	c.1570G>A	p.Ala524Thr	missense	Exon 1 of 1	ENSP00000474388.1	Q86UF2
ENSG00000291149	ENST00000700950.2		n.180+13009G>A		intron	N/A
ENSG00000291149	ENST00000838407.1		n.212+5695G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

77340

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000303

AC:

AN:

66094

AF XY:

0.0000298

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000418

AC:

AN:

23952

American (AMR)

AF:

0.0000957

AC:

AN:

20892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17358

East Asian (EAS)

AF:

0.00

AC:

AN:

34052

South Asian (SAS)

AF:

0.000198

AC:

AN:

55584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37916

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3036

European-Non Finnish (NFE)

AF:

0.00000749

AC:

AN:

801456

Other (OTH)

AF:

0.0000890

AC:

AN:

44936

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.323

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

African (AFR)

AF:

0.00

AC:

AN:

21526

American (AMR)

AF:

0.00

AC:

AN:

6328

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1828

East Asian (EAS)

AF:

0.00

AC:

AN:

2982

South Asian (SAS)

AF:

0.00

AC:

AN:

1632

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

36762

Other (OTH)

AF:

0.00

AC:

AN:

916

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.4

(source)

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

PhyloP100

0.96

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

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over