rs772922944

Variant names:

• chr7-143756049-A-G
• rs772922944
• NM_178561.5:c.1610T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_178561.5(CTAGE6):​c.1610T>C​(p.Leu537Pro) 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 5)
  • Exomes 𝑓: 0.00053 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTAGE6 NM_178561.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007961482).

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.1610T>C	p.Leu537Pro	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.1610T>C	p.Leu537Pro	missense	Exon 1 of 1	ENSP00000474388.1	Q86UF2
	ENSG00000291149	ENST00000700950.2		n.180+13049T>C		intron	N/A
	ENSG00000291149	ENST00000838407.1		n.212+5735T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 16 AN: 43480 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.000328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000599

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000940

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000439

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000860 AC: 48 AN: 55786 AF XY: 0.000890

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00248

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000519

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000756

Gnomad OTH exome AF: 0.000534

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000532 AC: 453 AN: 851972 Hom.: 3 Cov.: 12 AF XY: 0.000516 AC XY: 220 AN XY: 426206

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

African (AFR) AF: 0.000341 AC: 7 AN: 20554

American (AMR) AF: 0.00212 AC: 40 AN: 18872

Ashkenazi Jewish (ASJ) AF: 0.000127 AC: 2 AN: 15756

East Asian (EAS) AF: 0.000428 AC: 14 AN: 32730

South Asian (SAS) AF: 0.000417 AC: 21 AN: 50362

European-Finnish (FIN) AF: 0.0000954 AC: 3 AN: 31434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2656

European-Non Finnish (NFE) AF: 0.000546 AC: 350 AN: 640948

Other (OTH) AF: 0.000414 AC: 16 AN: 38660

⚠️ 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: 0.000345 AC: 15 AN: 43480 Hom.: 0 Cov.: 5 AF XY: 0.000313 AC XY: 6 AN XY: 19156

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

African (AFR) AF: 0.000245 AC: 3 AN: 12254

American (AMR) AF: 0.000598 AC: 2 AN: 3344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 982

East Asian (EAS) AF: 0.00 AC: 0 AN: 2022

South Asian (SAS) AF: 0.000945 AC: 1 AN: 1058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 160

European-Non Finnish (NFE) AF: 0.000439 AC: 9 AN: 20500

Other (OTH) AF: 0.00 AC: 0 AN: 542

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000471618), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000560 Hom.: 1

ExAC AF: 0.0000578 AC: 2

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	0.078
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.46
DEOGEN2	Benign	0.051	T
FATHMM_MKL	Benign	0.060	N
MetaRNN	Benign	0.0080	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.8
PrimateAI	Uncertain	0.58	T
Sift4G	Benign	0.28	T
Polyphen		0.35	B
Vest4		0.17
MVP		0.12
GERP RS		0.11
Varity_R		0.16
gMVP		0.64
Mutation Taster		=81/19	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: rs772922944; hg19: chr7-143453142;