chr7-143573145-A-G

Variant names:

• chr7-143573145-A-G
• rs1396002411
• NM_001008747.2:c.1328A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001008747.2(CTAGE15):​c.1328A>G​(p.Glu443Gly) 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 0.000017 (0 hom., cov: 16)
  • Exomes 𝑓: 0.0000040 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTAGE15 NM_001008747.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.99
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.42183325).

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.1328A>G	p.Glu443Gly	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.1328A>G	p.Glu443Gly	missense	Exon 1 of 1	ENSP00000474204.1	A4D2H0
	ENSG00000290786	ENST00000838653.1		n.88+12781A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000174 AC: 2 AN: 114970 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000504

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000178 AC: 2 AN: 112234 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000180

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: 0.00000398 AC: 5 AN: 1254890 Hom.: 0 Cov.: 30 AF XY: 0.00000320 AC XY: 2 AN XY: 625516

⚠️ 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: 28974

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22796

East Asian (EAS) AF: 0.0000836 AC: 3 AN: 35884

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 74340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4316

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 956398

Other (OTH) AF: 0.00 AC: 0 AN: 52256

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0300676), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000174 AC: 2 AN: 114970 Hom.: 0 Cov.: 16 AF XY: 0.0000361 AC XY: 2 AN XY: 55356

African (AFR) AF: 0.00 AC: 0 AN: 30652

American (AMR) AF: 0.00 AC: 0 AN: 10614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2790

East Asian (EAS) AF: 0.000504 AC: 2 AN: 3966

South Asian (SAS) AF: 0.00 AC: 0 AN: 3558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 54050

Other (OTH) AF: 0.00 AC: 0 AN: 1542

Alfa AF: 0.00 Hom.: 0

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	Benign	0.30
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Benign	0.72
DEOGEN2	Uncertain	0.44	T
FATHMM_MKL	Benign	0.14	N
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.42	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		3.0
PrimateAI	Uncertain	0.52	T
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.40
MVP		0.068
GERP RS		0.11
Varity_R		0.13
gMVP		0.27
Mutation Taster		=97/3	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: rs1396002411; hg19: chr7-143270238;