7-143573202-G-A

Variant names:

• chr7-143573202-G-A
• rs777753972
• NM_001008747.2:c.1385G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001008747.2(CTAGE15):​c.1385G>A​(p.Gly462Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.000036 (0 hom., cov: 12)
  • Exomes 𝑓: 0.00012 (22 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTAGE15 NM_001008747.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.371
• Publications: 0 publications found

Genes affected

CTAGE15 (HGNC:37295): (CTAGE family member 15) 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]

ENSG00000290786 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008276373).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008747.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTAGE15	NM_001008747.2	MANE Select	c.1385G>A	p.Gly462Glu	missense	Exon 1 of 1	NP_001008747.1	A4D2H0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTAGE15	ENST00000420911.2	TSL:6 MANE Select	c.1385G>A	p.Gly462Glu	missense	Exon 1 of 1	ENSP00000474204.1	A4D2H0
	ENSG00000290786	ENST00000838653.1		n.88+12838G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000358 AC: 3 AN: 83690 Hom.: 0 Cov.: 12

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00127

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000277 AC: 27 AN: 97406 AF XY: 0.000372

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000123 AC: 147 AN: 1198198 Hom.: 22 Cov.: 27 AF XY: 0.000184 AC XY: 110 AN XY: 598014

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

African (AFR) AF: 0.00 AC: 0 AN: 27420

American (AMR) AF: 0.00 AC: 0 AN: 34692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22154

East Asian (EAS) AF: 0.00 AC: 0 AN: 35446

South Asian (SAS) AF: 0.00193 AC: 140 AN: 72444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 908490

Other (OTH) AF: 0.000140 AC: 7 AN: 50174

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000358 AC: 3 AN: 83752 Hom.: 0 Cov.: 12 AF XY: 0.0000503 AC XY: 2 AN XY: 39728

African (AFR) AF: 0.00 AC: 0 AN: 22078

American (AMR) AF: 0.00 AC: 0 AN: 7180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2222

East Asian (EAS) AF: 0.00 AC: 0 AN: 2796

South Asian (SAS) AF: 0.00126 AC: 3 AN: 2372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 166

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 41160

Other (OTH) AF: 0.00 AC: 0 AN: 1062

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000320 AC: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.052	T
FATHMM_MKL	Benign	0.092	N
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.0083	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.37
PrimateAI	Uncertain	0.65	T
Sift4G	Benign	0.36	T
Polyphen		0.0090	B
Vest4		0.32
MVP		0.043
GERP RS		0.11
Varity_R		0.27
gMVP		0.48
Mutation Taster		=99/1	polymorphism

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: rs777753972; hg19: chr7-143270295;