7-143756568-T-G

Variant names:

• chr7-143756568-T-G
• rs77246673
• NM_178561.5:c.1091A>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.293
• Publications: 8 publications found

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]

ENSG00000291149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• 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 VariationId is 402570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 1220 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTAGE6	NM_178561.5	c.1091A>C	p.Glu364Ala	missense_variant	Exon 1 of 1	ENST00000470691.2	NP_848656.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTAGE6	ENST00000470691.2	c.1091A>C	p.Glu364Ala	missense_variant	Exon 1 of 1	6	NM_178561.5	ENSP00000474388.1

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

GnomAD2 exomes AF: 0.235 AC: 37761 AN: 160816 AF XY: 0.232

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.220 AC: 5431 AN: 24732

American (AMR) AF: 0.213 AC: 6613 AN: 31060

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 2405 AN: 19100

East Asian (EAS) AF: 0.150 AC: 4132 AN: 27560

South Asian (SAS) AF: 0.142 AC: 9198 AN: 64660

European-Finnish (FIN) AF: 0.111 AC: 4213 AN: 38110

Middle Eastern (MID) AF: 0.123 AC: 385 AN: 3136

European-Non Finnish (NFE) AF: 0.0660 AC: 58424 AN: 884624

Other (OTH) AF: 0.109 AC: 4965 AN: 45760

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.323 AC: 9410 AN: 29092

American (AMR) AF: 0.262 AC: 2755 AN: 10530

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 425 AN: 2406

East Asian (EAS) AF: 0.169 AC: 601 AN: 3556

South Asian (SAS) AF: 0.183 AC: 621 AN: 3392

European-Finnish (FIN) AF: 0.104 AC: 788 AN: 7604

Middle Eastern (MID) AF: 0.197 AC: 45 AN: 228

European-Non Finnish (NFE) AF: 0.160 AC: 7578 AN: 47340

Other (OTH) AF: 0.212 AC: 317 AN: 1498

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.162 Hom.: 73

ExAC AF: 0.220 AC: 26075

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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
PhyloP100		-0.29
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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