Variant 7-144185257-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_198495.3(CTAGE4):c.1754T>C(p.Ile585Thr) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 2)

Exomes 𝑓: 0.0031 ( 12 hom. )

Failed GnomAD Quality Control

Consequence

CTAGE4
NM_198495.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.05

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033382773).

BP6

Variant 7-144185257-T-C is Benign according to our data. Variant chr7-144185257-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2389311.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTAGE4	NM_198495.3 linkuse as main transcript	c.1754T>C	p.Ile585Thr	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.1754T>C	p.Ile585Thr	missense_variant	1/1		NM_198495.3	ENSP00000419539	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

7768

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00178

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00139

Gnomad SAS

AF:

0.00220

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000586

Gnomad OTH

AF:

0.00758

GnomAD3 exomes

AF:

0.00384

AC:

125

AN:

32514

Hom.:

AF XY:

0.00303

AC XY:

AN XY:

16492

show subpopulations

Gnomad AFR exome

AF:

0.0356

Gnomad AMR exome

AF:

0.00375

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000868

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00272

Gnomad NFE exome

AF:

0.000437

Gnomad OTH exome

AF:

0.00175

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00313

AC:

1211

AN:

387328

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

622

AN XY:

202792

show subpopulations

Gnomad4 AFR exome

AF:

0.0355

Gnomad4 AMR exome

AF:

0.00293

Gnomad4 ASJ exome

AF:

0.000170

Gnomad4 EAS exome

AF:

0.00240

Gnomad4 SAS exome

AF:

0.00418

Gnomad4 FIN exome

AF:

0.000719

Gnomad4 NFE exome

AF:

0.00205

Gnomad4 OTH exome

AF:

0.00370

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00297

AC:

AN:

7748

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

AN XY:

3582

show subpopulations

Gnomad4 AFR

AF:

0.0154

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00139

Gnomad4 SAS

AF:

0.00227

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000587

Gnomad4 OTH

AF:

0.00714

Alfa

AF:

0.00531

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.16

DANN

Benign

0.12

DEOGEN2

Benign

0.0025

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.52

M_CAP

Benign

0.0020

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

2.5

REVEL

Benign

0.038

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.016

MutPred

0.18

Gain of phosphorylation at I585 (P = 0.0023);

MVP

0.030

ClinPred

0.00043

Varity_R

0.036

gMVP

0.063

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