7-143573090-C-T

Variant summary

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

The NM_001008747.2(CTAGE15):​c.1273C>T​(p.Arg425Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/15 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. R425L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000032 ( 1 hom., cov: 17)
Exomes 𝑓: 0.000012 ( 2 hom. )
Failed GnomAD Quality Control

Consequence

CTAGE15
NM_001008747.2 missense

Scores

1
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75
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]

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=0.12251964).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CTAGE15NM_001008747.2 linkc.1273C>T p.Arg425Cys missense_variant Exon 1 of 1 ENST00000420911.2 NP_001008747.1 A4D2H0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CTAGE15ENST00000420911.2 linkc.1273C>T p.Arg425Cys missense_variant Exon 1 of 1 6 NM_001008747.2 ENSP00000474204.1 A4D2H0

Frequencies

GnomAD3 genomes
AF:
0.0000323
AC:
4
AN:
123694
Hom.:
1
Cov.:
17
show subpopulations
Gnomad AFR
AF:
0.0000905
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000861
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
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000125
AC:
16
AN:
1285036
Hom.:
2
Cov.:
33
AF XY:
0.0000125
AC XY:
8
AN XY:
639336
show subpopulations
Gnomad4 AFR exome
AF:
0.0000335
Gnomad4 AMR exome
AF:
0.0000266
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000111
Gnomad4 SAS exome
AF:
0.0000131
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000918
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000323
AC:
4
AN:
123694
Hom.:
1
Cov.:
17
AF XY:
0.0000167
AC XY:
1
AN XY:
59738
show subpopulations
Gnomad4 AFR
AF:
0.0000905
Gnomad4 AMR
AF:
0.0000861
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
ExAC
AF:
0.00000914
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 07, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1273C>T (p.R425C) alteration is located in exon 1 (coding exon 1) of the CTAGE15 gene. This alteration results from a C to T substitution at nucleotide position 1273, causing the arginine (R) at amino acid position 425 to be replaced by a cysteine (C). 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
0.10
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
18
DANN
Benign
0.28
DEOGEN2
Benign
0.013
T
FATHMM_MKL
Benign
0.054
N
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.12
T
MutationAssessor
Benign
0.90
L
PrimateAI
Benign
0.46
T
Sift4G
Uncertain
0.036
D
Polyphen
0.90
P
Vest4
0.058
MVP
0.043
GERP RS
0.11
Varity_R
0.17
gMVP
0.055

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.

Other links and lift over

dbSNP: rs760763266; hg19: chr7-143270183; COSMIC: COSV101372145; COSMIC: COSV101372145; API