Genetic Variant NM_001008747.2:c.1345C>T (chr7-143573162-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001008747.2(CTAGE15):c.1345C>T(p.His449Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000093 ( 0 hom., cov: 16)

Exomes 𝑓: 8.2e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CTAGE15
NM_001008747.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

Publications

0 publications found

Variant links:

Genes affected

CTAGE15 (HGNC:37295): (CTAGE family member 15) 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]

CTAGE15 links:

ENSG00000290786 (HGNC:):

ENSG00000290786 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19737798).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008747.2. 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
	CTAGE15	NM_001008747.2	MANE Select	c.1345C>T	p.His449Tyr	missense	Exon 1 of 1	NP_001008747.1	A4D2H0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTAGE15	ENST00000420911.2	TSL:6 MANE Select	c.1345C>T	p.His449Tyr	missense	Exon 1 of 1	ENSP00000474204.1	A4D2H0
	ENSG00000290786	ENST00000838653.1		n.88+12798C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000927

AC:

AN:

107890

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:

0.00

Gnomad OTH

AF:

0.000698

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

8.17e-7

AC:

AN:

1223374

Hom.:

Cov.:

AF XY:

0.00000164

AC XY:

AN XY:

610706

show subpopulations

African (AFR)

AF:

0.0000360

AC:

AN:

27778

American (AMR)

AF:

0.00

AC:

AN:

33518

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22152

East Asian (EAS)

AF:

0.00

AC:

AN:

35748

South Asian (SAS)

AF:

0.00

AC:

AN:

72728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3940

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

932404

Other (OTH)

AF:

0.00

AC:

AN:

51100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.775

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

AF:

0.00000926

AC:

AN:

107948

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

51884

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28758

American (AMR)

AF:

0.00

AC:

AN:

9798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3650

South Asian (SAS)

AF:

0.00

AC:

AN:

3294

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6188

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51246

Other (OTH)

AF:

0.000690

AC:

AN:

1450

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.061

FATHMM_MKL

Benign

0.040

M_CAP

Benign

0.0050

MetaRNN

Benign

0.20

MutationAssessor

Uncertain

2.1

PhyloP100

1.3

PrimateAI

Uncertain

0.54

Sift4G

Uncertain

0.057

Polyphen

0.88

Vest4

0.14

MVP

0.043

GERP RS

-0.22

Varity_R

0.12

gMVP

0.065

Mutation Taster

=98/2

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