Variant 7-144185245-A-G 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.1742A>G(p.Tyr581Cys) 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 0.0036 ( 0 hom., cov: 1)

Exomes 𝑓: 0.0034 ( 11 hom. )

Failed GnomAD Quality Control

Consequence

CTAGE4
NM_198495.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0440

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=0.0034122467).

BP6

Variant 7-144185245-A-G is Benign according to our data. Variant chr7-144185245-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2411330.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.1742A>G	p.Tyr581Cys	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.1742A>G	p.Tyr581Cys	missense_variant	1/1		NM_198495.3	ENSP00000419539	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

5336

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00370

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00284

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000861

Gnomad OTH

AF:

0.00962

GnomAD3 exomes

AF:

0.00399

AC:

124

AN:

31062

Hom.:

AF XY:

0.00331

AC XY:

AN XY:

15698

show subpopulations

Gnomad AFR exome

AF:

0.0337

Gnomad AMR exome

AF:

0.00299

Gnomad ASJ exome

AF:

0.00343

Gnomad EAS exome

AF:

0.00126

Gnomad SAS exome

AF:

0.00190

Gnomad FIN exome

AF:

0.00279

Gnomad NFE exome

AF:

0.000551

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00339

AC:

1239

AN:

365554

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

643

AN XY:

191646

show subpopulations

Gnomad4 AFR exome

AF:

0.0358

Gnomad4 AMR exome

AF:

0.00258

Gnomad4 ASJ exome

AF:

0.00418

Gnomad4 EAS exome

AF:

0.00225

Gnomad4 SAS exome

AF:

0.00480

Gnomad4 FIN exome

AF:

0.000821

Gnomad4 NFE exome

AF:

0.00213

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00357

AC:

AN:

5326

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

AN XY:

2482

show subpopulations

Gnomad4 AFR

AF:

0.0171

Gnomad4 AMR

AF:

0.00369

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00289

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000863

Gnomad4 OTH

AF:

0.00909

Alfa

AF:

0.00565

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

Apr 13, 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

0.047

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.3

DANN

Benign

0.19

DEOGEN2

Benign

0.0035

Eigen

Benign

-2.0

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00051

LIST_S2

Benign

0.22

M_CAP

Benign

0.0013

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.92

REVEL

Benign

0.028

Sift

Benign

0.98

Sift4G

Benign

0.18

Polyphen

0.0

Vest4

0.093

MutPred

0.18

Loss of phosphorylation at Y581 (P = 0.0225);

MVP

0.067

ClinPred

0.0013

Varity_R

0.035

gMVP

0.13

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