chr7-143756089-C-G

Variant names:

• chr7-143756089-C-G
• rs764189306
• NM_178561.5:c.1570G>C

Variant summary

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

The NM_178561.5(CTAGE6):​c.1570G>C​(p.Ala524Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A524S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 9)
  • Exomes 𝑓: 9.6e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTAGE6 NM_178561.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.965
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09675643).

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.1570G>C	p.Ala524Pro	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.1570G>C	p.Ala524Pro	missense	Exon 1 of 1	ENSP00000474388.1	Q86UF2
	ENSG00000291149	ENST00000700950.2		n.180+13009G>C		intron	N/A
	ENSG00000291149	ENST00000838407.1		n.212+5695G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.62e-7 AC: 1 AN: 1039200 Hom.: 0 Cov.: 17 AF XY: 0.00000194 AC XY: 1 AN XY: 515710

⚠️ 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: 23952

American (AMR) AF: 0.00 AC: 0 AN: 20892

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17358

East Asian (EAS) AF: 0.0000294 AC: 1 AN: 34052

South Asian (SAS) AF: 0.00 AC: 0 AN: 55584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3036

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 801472

Other (OTH) AF: 0.00 AC: 0 AN: 44936

⚠️ 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 Cov.: 9

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.6
DANN	Benign	0.32
DEOGEN2	Benign	0.070	T
FATHMM_MKL	Benign	0.019	N
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.097	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.96
PrimateAI	Uncertain	0.50	T
Sift4G	Benign	0.20	T
Polyphen		0.58	P
Vest4		0.11
MVP		0.14
GERP RS		-0.22
Varity_R		0.10
gMVP		0.44
Mutation Taster		=96/4	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: rs764189306; hg19: chr7-143453182;