7-143755801-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2 BP4_Strong BP6_Moderate

The NM_178561.5(CTAGE6):c.1858G>A(p.Ala620Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (0 hom., cov: 0)
  • Exomes 𝑓: 0.042 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTAGE6 NM_178561.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.245

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 Likely_benign. Variant got -5 ACMG points.

• PP2: Missense variant where missense usually causes diseases, CTAGE6
• BP4: Computational evidence support a benign effect (MetaRNN=0.001861155).
• BP6: Variant 7-143755801-C-T is Benign according to our data. Variant chr7-143755801-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2391468.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTAGE6	NM_178561.5	c.1858G>A	p.Ala620Thr	missense_variant	1/1	ENST00000470691.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTAGE6	ENST00000470691.2	c.1858G>A	p.Ala620Thr	missense_variant	1/1		NM_178561.5	P1
	ENST00000700950.1	n.178+13297G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 4 Hom.: 0 Cov.: 0 FAILED QC

Gnomad NFE AF: 0.250

GnomAD3 exomes AF: 0.0322 AC: 416 AN: 12938 Hom.: 1 AF XY: 0.0304 AC XY: 215 AN XY: 7072

Gnomad AFR exome AF: 0.0517

Gnomad AMR exome AF: 0.0398

Gnomad ASJ exome AF: 0.0380

Gnomad EAS exome AF: 0.00434

Gnomad SAS exome AF: 0.0168

Gnomad FIN exome AF: 0.0269

Gnomad NFE exome AF: 0.0546

Gnomad OTH exome AF: 0.0399

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0417 AC: 3796 AN: 91002 Hom.: 2 Cov.: 0 AF XY: 0.0402 AC XY: 1869 AN XY: 46550

Gnomad4 AFR exome AF: 0.0567

Gnomad4 AMR exome AF: 0.0362

Gnomad4 ASJ exome AF: 0.0490

Gnomad4 EAS exome AF: 0.00253

Gnomad4 SAS exome AF: 0.0156

Gnomad4 FIN exome AF: 0.0339

Gnomad4 NFE exome AF: 0.0489

Gnomad4 OTH exome AF: 0.0418

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE AF: 0.250

Alfa AF: 0.0180 Hom.: 0

ExAC AF: 0.00470 AC: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 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	0.074
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	11
Dann	Benign	0.59
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.020	N
MetaRNN	Benign	0.0019	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.20	T
Polyphen		0.32	B
Vest4		0.016
GERP RS		0.11
Varity_R		0.055
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs752981800; hg19: chr7-143452894;