Variant chr7-143756073-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong

The NM_178561.5(CTAGE6):c.1586G>A(p.Arg529His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 8)

Exomes 𝑓: 0.000032 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CTAGE6
NM_178561.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

Variant links:

Genes affected

CTAGE6 (HGNC:28644): (CTAGE family member 6) 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]

CTAGE6 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant where missense usually causes diseases, CTAGE6

BP4

Computational evidence support a benign effect (MetaRNN=0.04818356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTAGE6	NM_178561.5 linkuse as main transcript	c.1586G>A	p.Arg529His	missense_variant	1/1	ENST00000470691.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTAGE6	ENST00000470691.2 linkuse as main transcript	c.1586G>A	p.Arg529His	missense_variant	1/1		NM_178561.5	P1
	ENST00000700950.1 linkuse as main transcript	n.178+13025G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

67228

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000586

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000186

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:

0.0000313

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000488

AC:

AN:

61536

Hom.:

AF XY:

0.0000962

AC XY:

AN XY:

31188

show subpopulations

Gnomad AFR exome

AF:

0.000539

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000321

AC:

AN:

965350

Hom.:

Cov.:

AF XY:

0.0000313

AC XY:

AN XY:

479904

show subpopulations

Gnomad4 AFR exome

AF:

0.000976

Gnomad4 AMR exome

AF:

0.0000510

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000812

Gnomad4 OTH exome

AF:

0.0000471

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000193

AC:

AN:

67284

Hom.:

Cov.:

AF XY:

0.0000993

AC XY:

AN XY:

30218

show subpopulations

Gnomad4 AFR

AF:

0.000583

Gnomad4 AMR

AF:

0.000186

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000313

Gnomad4 OTH

AF:

0.00

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

Mar 29, 2022

The c.1586G>A (p.R529H) alteration is located in exon 1 (coding exon 1) of the CTAGE6 gene. This alteration results from a G to A substitution at nucleotide position 1586, causing the arginine (R) at amino acid position 529 to be replaced by a histidine (H). 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

0.095

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.28

DEOGEN2

Benign

0.032

FATHMM_MKL

Benign

0.016

M_CAP

Benign

0.013

MetaRNN

Benign

0.048

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.52

Sift4G

Benign

0.50

Polyphen

0.32

Vest4

0.053

MVP

0.14

GERP RS

0.11

Varity_R

0.048

gMVP

0.40

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