7-143756568-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2 BP4_Strong BP6_Moderate BA1

The NM_178561.5(CTAGE6):c.1091A>C(p.Glu364Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 106,248 control chromosomes in the GnomAD database, including 1,220 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (1220 hom., cov: 29)
  • Exomes 𝑓: 0.084 (8583 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTAGE6 NM_178561.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.293

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• PP2: Missense variant where missense usually causes diseases, CTAGE6
• BP4: Computational evidence support a benign effect (MetaRNN=0.0024744868).
• BP6: Variant 7-143756568-T-G is Benign according to our data. Variant chr7-143756568-T-G is described in ClinVar as [Benign]. Clinvar id is 402570.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTAGE6	NM_178561.5	c.1091A>C	p.Glu364Ala	missense_variant	1/1	ENST00000470691.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTAGE6	ENST00000470691.2	c.1091A>C	p.Glu364Ala	missense_variant	1/1		NM_178561.5	P1
	ENST00000700950.1	n.178+12530A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.213 AC: 22579 AN: 106158 Hom.: 1218 Cov.: 29

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.189

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.211

GnomAD3 exomes AF: 0.235 AC: 37761 AN: 160816 Hom.: 1845 AF XY: 0.232 AC XY: 20095 AN XY: 86656

Gnomad AFR exome AF: 0.350

Gnomad AMR exome AF: 0.304

Gnomad ASJ exome AF: 0.231

Gnomad EAS exome AF: 0.201

Gnomad SAS exome AF: 0.229

Gnomad FIN exome AF: 0.186

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.230

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0841 AC: 95766 AN: 1138742 Hom.: 8583 Cov.: 34 AF XY: 0.0871 AC XY: 49162 AN XY: 564202

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0660

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.213 AC: 22612 AN: 106248 Hom.: 1220 Cov.: 29 AF XY: 0.213 AC XY: 11082 AN XY: 52060

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.212

Alfa AF: 0.162 Hom.: 73

ExAC AF: 0.220 AC: 26075

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Fails inbreeding coefficient filter -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.042
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	1.1
Dann	Benign	0.51
DEOGEN2	Benign	0.0039	T
FATHMM_MKL	Benign	0.00039	N
MetaRNN	Benign	0.0025	T
MutationAssessor	Benign	-3.0	N
PrimateAI	Uncertain	0.55	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.032
GERP RS		0.11
Varity_R		0.084
gMVP		0.064

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

Other links and lift over

dbSNP: rs77246673; hg19: chr7-143453661; COSMIC: COSV69916501; COSMIC: COSV69916501;