7-143756350-C-T

Variant names:

• chr7-143756350-C-T
• rs370904742
• NM_178561.5:c.1309G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_178561.5(CTAGE6):​c.1309G>A​(p.Ala437Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000337 in 1,455,018 control chromosomes in the GnomAD database, including 6 homozygotes. 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 0.0 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000034 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTAGE6 NM_178561.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13188383).
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

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.1309G>A	p.Ala437Thr	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.1309G>A	p.Ala437Thr	missense	Exon 1 of 1	ENSP00000474388.1	Q86UF2
	ENSG00000291149	ENST00000700950.2		n.180+12748G>A		intron	N/A
	ENSG00000291149	ENST00000838407.1		n.212+5434G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151000 Hom.: 0 Cov.: 24

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000605 AC: 15 AN: 247960 AF XY: 0.0000817

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: 0.0000267

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000337 AC: 49 AN: 1455018 Hom.: 6 Cov.: 31 AF XY: 0.0000401 AC XY: 29 AN XY: 723824

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

African (AFR) AF: 0.0000301 AC: 1 AN: 33232

American (AMR) AF: 0.00 AC: 0 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.000398 AC: 34 AN: 85462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.000752 AC: 4 AN: 5318

European-Non Finnish (NFE) AF: 0.00000722 AC: 8 AN: 1107300

Other (OTH) AF: 0.0000333 AC: 2 AN: 60058

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000000688338), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151000 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 73776

African (AFR) AF: 0.00 AC: 0 AN: 41024

American (AMR) AF: 0.00 AC: 0 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67620

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.0000936 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.0000829 AC: 10

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	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Benign	0.83
DEOGEN2	Benign	0.072	T
FATHMM_MKL	Benign	0.046	N
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.13	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.3
PrimateAI	Uncertain	0.53	T
Sift4G	Benign	0.27	T
Polyphen		0.79	P
Vest4		0.18
MVP		0.30
GERP RS		0.11
Varity_R		0.069
gMVP		0.28
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: rs370904742; hg19: chr7-143453443;