NM_178561.5:c.1573C>T

Variant names:

• chr7-143756086-G-A
• rs1260726556
• NM_178561.5:c.1573C>T

Variant summary

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

The NM_178561.5(CTAGE6):​c.1573C>T​(p.Pro525Ser) 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 9)
  • Exomes 𝑓: 0.0000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTAGE6 NM_178561.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.95
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14440522).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178561.5. 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
	CTAGE6	NM_178561.5	MANE Select	c.1573C>T	p.Pro525Ser	missense	Exon 1 of 1	NP_848656.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTAGE6	ENST00000470691.2	TSL:6 MANE Select	c.1573C>T	p.Pro525Ser	missense	Exon 1 of 1	ENSP00000474388.1	Q86UF2
	ENSG00000291149	ENST00000700950.2		n.180+13012C>T		intron	N/A
	ENSG00000291149	ENST00000838407.1		n.212+5698C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 1 AN: 75790 Hom.: 0 Cov.: 9

Gnomad AFR AF: 0.0000474

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000303 AC: 2 AN: 66014 AF XY: 0.00

Gnomad AFR exome AF: 0.000351

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: 0.00000194 AC: 2 AN: 1030548 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 511682

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

African (AFR) AF: 0.0000840 AC: 2 AN: 23808

American (AMR) AF: 0.00 AC: 0 AN: 20808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17310

East Asian (EAS) AF: 0.00 AC: 0 AN: 33996

South Asian (SAS) AF: 0.00 AC: 0 AN: 55548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3020

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 793810

Other (OTH) AF: 0.00 AC: 0 AN: 44608

⚠️ 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: 0.0000132 AC: 1 AN: 75862 Hom.: 0 Cov.: 9 AF XY: 0.0000291 AC XY: 1 AN XY: 34378

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

African (AFR) AF: 0.0000472 AC: 1 AN: 21206

American (AMR) AF: 0.00 AC: 0 AN: 6154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1796

East Asian (EAS) AF: 0.00 AC: 0 AN: 2940

South Asian (SAS) AF: 0.00 AC: 0 AN: 1604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 210

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 36016

Other (OTH) AF: 0.00 AC: 0 AN: 908

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	0.084
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.42
DEOGEN2	Benign	0.25	T
FATHMM_MKL	Benign	0.12	N
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.14	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.9
PrimateAI	Benign	0.45	T
Sift4G	Benign	0.21	T
Polyphen		0.38	B
Vest4		0.14
MVP		0.37
GERP RS		0.11
Varity_R		0.069
gMVP		0.49
Mutation Taster		=94/6	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: rs1260726556; hg19: chr7-143453179;