7-143755846-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_178561.5(CTAGE6):c.1813T>C(p.Cys605Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0045 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTAGE6 NM_178561.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.483

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 -9 ACMG points.

• PP2: Missense variant where missense usually causes diseases, CTAGE6
• BP4: Computational evidence support a benign effect (MetaRNN=0.0035294294).
• BP6: Variant 7-143755846-A-G is Benign according to our data. Variant chr7-143755846-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2230026.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTAGE6	NM_178561.5	c.1813T>C	p.Cys605Arg	missense_variant	1/1	ENST00000470691.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTAGE6	ENST00000470691.2	c.1813T>C	p.Cys605Arg	missense_variant	1/1		NM_178561.5	P1
	ENST00000700950.1	n.178+13252T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 30 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00

Gnomad EAS AF: 0.00

Gnomad NFE AF: 0.00

GnomAD3 exomes AF: 0.00782 AC: 185 AN: 23648 Hom.: 2 AF XY: 0.00833 AC XY: 104 AN XY: 12478

Gnomad AFR exome AF: 0.0195

Gnomad AMR exome AF: 0.00632

Gnomad ASJ exome AF: 0.00364

Gnomad EAS exome AF: 0.00667

Gnomad SAS exome AF: 0.0235

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000829

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00446 AC: 849 AN: 190460 Hom.: 3 Cov.: 0 AF XY: 0.00558 AC XY: 552 AN XY: 98980

Gnomad4 AFR exome AF: 0.0183

Gnomad4 AMR exome AF: 0.00487

Gnomad4 ASJ exome AF: 0.00157

Gnomad4 EAS exome AF: 0.00552

Gnomad4 SAS exome AF: 0.0214

Gnomad4 FIN exome AF: 0.000554

Gnomad4 NFE exome AF: 0.00126

Gnomad4 OTH exome AF: 0.00509

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 AFR AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 NFE AF: 0.00

Alfa AF: 0.00202 Hom.: 0

ExAC AF: 0.00112 AC: 1

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 25, 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	0.041
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	0.10
Dann	Benign	0.11
DEOGEN2	Benign	0.0029	T
FATHMM_MKL	Benign	0.00040	N
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.0035	T
MutationAssessor	Benign	-0.58	N
PrimateAI	Benign	0.44	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.025
MVP		0.014
GERP RS		-0.22
Varity_R		0.26
gMVP		0.14

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: rs751783371; hg19: chr7-143452939;