Variant chr7-144185371-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198495.3(CTAGE4):c.1868C>T(p.Pro623Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 6)

Exomes 𝑓: 0.0031 ( 16 hom. )

Failed GnomAD Quality Control

Consequence

CTAGE4
NM_198495.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.298

Variant links:

Genes affected

CTAGE4 (HGNC:24772): (CTAGE family member 4) 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]

CTAGE4 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=0.0059865415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTAGE4	NM_198495.3 linkuse as main transcript	c.1868C>T	p.Pro623Leu	missense_variant	1/1	ENST00000486333.2	NP_940897.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTAGE4	ENST00000486333.2 linkuse as main transcript	c.1868C>T	p.Pro623Leu	missense_variant	1/1		NM_198495.3	ENSP00000419539	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

47598

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000559

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000700

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00141

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00250

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00312

AC:

2444

AN:

783170

Hom.:

Cov.:

AF XY:

0.00309

AC XY:

1221

AN XY:

394880

show subpopulations

Gnomad4 AFR exome

AF:

0.000789

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00323

Gnomad4 FIN exome

AF:

0.000123

Gnomad4 NFE exome

AF:

0.00384

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00145

AC:

AN:

47644

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

AN XY:

22418

show subpopulations

Gnomad4 AFR

AF:

0.000557

Gnomad4 AMR

AF:

0.000697

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00141

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00143

Hom.:

ExAC

AF:

0.000216

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.1868C>T (p.P623L) alteration is located in exon 1 (coding exon 1) of the CTAGE4 gene. This alteration results from a C to T substitution at nucleotide position 1868, causing the proline (P) at amino acid position 623 to be replaced by a leucine (L). 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

0.077

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.3

DANN

Benign

0.83

DEOGEN2

Benign

0.028

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.85

M_CAP

Benign

0.0028

MetaRNN

Benign

0.0060

MetaSVM

Benign

-0.97

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.047

Sift

Benign

0.046

Sift4G

Uncertain

0.051

Polyphen

0.033

Vest4

0.17

MutPred

0.29

Loss of catalytic residue at P622 (P = 0.0175);

MVP

0.26

ClinPred

0.0035

Varity_R

0.056

gMVP

0.14

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