7-143755801-C-T

Variant names:

• chr7-143755801-C-T
• rs752981800
• NM_178561.5:c.1858G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_178561.5(CTAGE6):​c.1858G>A​(p.Ala620Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (0 hom., cov: 0)
  • Exomes 𝑓: 0.042 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTAGE6 NM_178561.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.245
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001861155).
• BP6: Variant 7-143755801-C-T is Benign according to our data. Variant chr7-143755801-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2391468.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1858G>A	p.Ala620Thr	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.1858G>A	p.Ala620Thr	missense	Exon 1 of 1	ENSP00000474388.1	Q86UF2
	ENSG00000291149	ENST00000700950.2		n.180+13297G>A		intron	N/A
	ENSG00000291149	ENST00000838407.1		n.212+5983G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0

Gnomad NFE AF: 0.250

GnomAD2 exomes AF: 0.0322 AC: 416 AN: 12938 AF XY: 0.0304

Gnomad AFR exome AF: 0.0517

Gnomad AMR exome AF: 0.0398

Gnomad ASJ exome AF: 0.0380

Gnomad EAS exome AF: 0.00434

Gnomad FIN exome AF: 0.0269

Gnomad NFE exome AF: 0.0546

Gnomad OTH exome AF: 0.0399

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0417 AC: 3796 AN: 91002 Hom.: 2 Cov.: 0 AF XY: 0.0402 AC XY: 1869 AN XY: 46550

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

African (AFR) AF: 0.0567 AC: 175 AN: 3084

American (AMR) AF: 0.0362 AC: 155 AN: 4278

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 97 AN: 1978

East Asian (EAS) AF: 0.00253 AC: 15 AN: 5928

South Asian (SAS) AF: 0.0156 AC: 122 AN: 7808

European-Finnish (FIN) AF: 0.0339 AC: 149 AN: 4392

Middle Eastern (MID) AF: 0.0833 AC: 26 AN: 312

European-Non Finnish (NFE) AF: 0.0489 AC: 2844 AN: 58122

Other (OTH) AF: 0.0418 AC: 213 AN: 5100

⚠️ 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: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

⚠️ 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: 0.0180 Hom.: 0

ExAC AF: 0.00470 AC: 2

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.074
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.59
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.020	N
MetaRNN	Benign	0.0019	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.24
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.20	T
Polyphen		0.32	B
Vest4		0.016
GERP RS		0.11
Varity_R		0.055
gMVP		0.15
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs752981800; hg19: chr7-143452894;