7-143756427-T-C

Variant names:

• chr7-143756427-T-C
• NM_178561.5:c.1232A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178561.5(CTAGE6):​c.1232A>G​(p.Glu411Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 25)
• Consequence: CTAGE6 NM_178561.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2893914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTAGE6	NM_178561.5	c.1232A>G	p.Glu411Gly	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.1232A>G	p.Glu411Gly	missense_variant	Exon 1 of 1	6	NM_178561.5	ENSP00000474388.1
ENSG00000291149	ENST00000700950.1	n.178+12671A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1232A>G (p.E411G) alteration is located in exon 1 (coding exon 1) of the CTAGE6 gene. This alteration results from a A to G substitution at nucleotide position 1232, causing the glutamic acid (E) at amino acid position 411 to be replaced by a glycine (G). 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	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.19
DEOGEN2	Benign	0.28	T
FATHMM_MKL	Benign	0.062	N
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.29	T
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.21	T
Polyphen		0.97	D
Vest4		0.13
MVP		0.22
GERP RS		0.11
Varity_R		0.085
gMVP		0.068

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-143453520;