rs760763266

Variant names:

• chr7-143573090-C-T
• rs760763266
• NM_001008747.2:c.1273C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001008747.2(CTAGE15):​c.1273C>T​(p.Arg425Cys) 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R425H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000032 (1 hom., cov: 17)
  • Exomes 𝑓: 0.000012 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTAGE15 NM_001008747.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75
• Publications: 1 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12251964).

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.1273C>T	p.Arg425Cys	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.1273C>T	p.Arg425Cys	missense	Exon 1 of 1	ENSP00000474204.1	A4D2H0
	ENSG00000290786	ENST00000838653.1		n.88+12726C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000323 AC: 4 AN: 123694 Hom.: 1 Cov.: 17

Gnomad AFR AF: 0.0000905

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000861

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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: 0.0000184 AC: 4 AN: 217914 AF XY: 0.0000338

Gnomad AFR exome AF: 0.0000730

Gnomad AMR exome AF: 0.0000345

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000599

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: 0.0000125 AC: 16 AN: 1285036 Hom.: 2 Cov.: 33 AF XY: 0.0000125 AC XY: 8 AN XY: 639336

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

African (AFR) AF: 0.0000335 AC: 1 AN: 29820

American (AMR) AF: 0.0000266 AC: 1 AN: 37596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23254

East Asian (EAS) AF: 0.000111 AC: 4 AN: 36004

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4580

European-Non Finnish (NFE) AF: 0.00000918 AC: 9 AN: 979916

Other (OTH) AF: 0.00 AC: 0 AN: 53296

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000214218), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000323 AC: 4 AN: 123694 Hom.: 1 Cov.: 17 AF XY: 0.0000167 AC XY: 1 AN XY: 59738

African (AFR) AF: 0.0000905 AC: 3 AN: 33158

American (AMR) AF: 0.0000861 AC: 1 AN: 11608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2966

East Asian (EAS) AF: 0.00 AC: 0 AN: 4300

South Asian (SAS) AF: 0.00 AC: 0 AN: 3862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 57462

Other (OTH) AF: 0.00 AC: 0 AN: 1666

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000914 AC: 1

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	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.28
DEOGEN2	Benign	0.013	T
FATHMM_MKL	Benign	0.054	N
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.7
PrimateAI	Benign	0.46	T
Sift4G	Uncertain	0.036	D
Polyphen		0.90	P
Vest4		0.058
MVP		0.043
GERP RS		0.11
Varity_R		0.17
gMVP		0.055
Mutation Taster		=100/0	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: rs760763266; hg19: chr7-143270183; COSMIC: COSV101372145; COSMIC: COSV101372145;