Genetic Variant CTAGE15:p.Arg425Cys (chr7-143573090-C-T) – ACMG Classification: Likely_benign (-2 pts)

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

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]

CTAGE15 links:

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
CTAGE15	NM_001008747.2 link	c.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
CTAGE15	ENST00000420911.2 link	c.1273C>T	p.Arg425Cys	missense_variant	Exon 1 of 1	6	NM_001008747.2	ENSP00000474204.1		A4D2H0

Frequencies

GnomAD3 genomes

AF:

0.0000323

AC:

AN:

123694

Hom.:

Cov.:

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:

AN:

1285036

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

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:

AN:

123694

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

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:

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

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.28

DEOGEN2

Benign

0.013

FATHMM_MKL

Benign

0.054

M_CAP

Benign

0.012

MetaRNN

Benign

0.12

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.46

Sift4G

Uncertain

0.036

Polyphen

0.90

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.

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