7-143756197-G-A

Variant names:

• chr7-143756197-G-A
• rs747659648
• NM_178561.5:c.1462C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_178561.5(CTAGE6):​c.1462C>T​(p.Gln488*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.000015 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTAGE6 NM_178561.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• 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_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.374 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

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.1462C>T	p.Gln488*	stop_gained	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.1462C>T	p.Gln488*	stop_gained	Exon 1 of 1	ENSP00000474388.1	Q86UF2
	ENSG00000291149	ENST00000700950.2		n.180+12901C>T		intron	N/A
	ENSG00000291149	ENST00000838407.1		n.212+5587C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.0000384 AC: 6 AN: 156190 AF XY: 0.0000354

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: 0.0000834

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000150 AC: 21 AN: 1404408 Hom.: 2 Cov.: 30 AF XY: 0.0000187 AC XY: 13 AN XY: 695538

⚠️ 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: 31132

American (AMR) AF: 0.00 AC: 0 AN: 35438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24228

East Asian (EAS) AF: 0.00 AC: 0 AN: 39252

South Asian (SAS) AF: 0.00 AC: 0 AN: 77948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3888

European-Non Finnish (NFE) AF: 0.0000194 AC: 21 AN: 1082828

Other (OTH) AF: 0.00 AC: 0 AN: 57760

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000225284), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000886 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	28
DANN	Benign	0.88
FATHMM_MKL	Benign	0.10	N
PhyloP100		1.7
Vest4		0.020
GERP RS		0.11
Mutation Taster		=142/58	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: rs747659648; hg19: chr7-143453290;