Variant chr7-144185541-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_198495.3(CTAGE4):c.2038T>G(p.Ser680Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 7 hom., cov: 18)

Exomes 𝑓: 0.0018 ( 72 hom. )

Failed GnomAD Quality Control

Consequence

CTAGE4
NM_198495.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.00400

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007178098).

BP6

Variant 7-144185541-T-G is Benign according to our data. Variant chr7-144185541-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2558585.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTAGE4	NM_198495.3 linkuse as main transcript	c.2038T>G	p.Ser680Ala	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.2038T>G	p.Ser680Ala	missense_variant	1/1		NM_198495.3	ENSP00000419539	P1

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

164

AN:

129130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000861

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000148

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000114

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00226

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000950

AC:

183

AN:

192712

Hom.:

AF XY:

0.000990

AC XY:

104

AN XY:

105008

show subpopulations

Gnomad AFR exome

AF:

0.000171

Gnomad AMR exome

AF:

0.000177

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000407

Gnomad NFE exome

AF:

0.00197

Gnomad OTH exome

AF:

0.000659

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00181

AC:

2537

AN:

1403150

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

1213

AN XY:

698650

show subpopulations

Gnomad4 AFR exome

AF:

0.000341

Gnomad4 AMR exome

AF:

0.000159

Gnomad4 ASJ exome

AF:

0.0000401

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000232

Gnomad4 NFE exome

AF:

0.00231

Gnomad4 OTH exome

AF:

0.000845

GnomAD4 genome

AF:

0.00127

AC:

164

AN:

129188

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

AN XY:

62708

show subpopulations

Gnomad4 AFR

AF:

0.000859

Gnomad4 AMR

AF:

0.000147

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000114

Gnomad4 NFE

AF:

0.00226

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00140

Hom.:

ExAC

AF:

0.00101

AC:

113

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2023

The c.2038T>G (p.S680A) alteration is located in exon 1 (coding exon 1) of the CTAGE4 gene. This alteration results from a T to G substitution at nucleotide position 2038, causing the serine (S) at amino acid position 680 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

CTAGE4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.67

CADD

Benign

9.5

DANN

Benign

0.92

DEOGEN2

Benign

0.016

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.57

M_CAP

Benign

0.0011

MetaRNN

Benign

0.0072

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.1

REVEL

Benign

0.071

Sift

Uncertain

0.024

Sift4G

Benign

0.70

Polyphen

0.010

Vest4

0.13

MVP

0.055

ClinPred

0.0054

Varity_R

0.15

gMVP

0.069

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