7-144184333-A-C

Position:

• chr7-144184333-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_198495.3(CTAGE4):​c.830A>C​(p.Lys277Thr) 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: not found (cov: 11)
  • Exomes 𝑓: 0.0000046 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTAGE4 NM_198495.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0930

Genes affected

CTAGE4 (HGNC:24772): (CTAGE family member 4) 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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21738967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTAGE4	NM_198495.3	c.830A>C	p.Lys277Thr	missense_variant	1/1	ENST00000486333.2	NP_940897.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTAGE4	ENST00000486333.2	c.830A>C	p.Lys277Thr	missense_variant	1/1		NM_198495.3	ENSP00000419539	P1

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000459 AC: 4 AN: 870642 Hom.: 0 Cov.: 12 AF XY: 0.00000894 AC XY: 4 AN XY: 447274

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000619

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 11

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

The c.830A>C (p.K277T) alteration is located in exon 1 (coding exon 1) of the CTAGE4 gene. This alteration results from a A to C substitution at nucleotide position 830, causing the lysine (K) at amino acid position 277 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.054
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.015	D
Polyphen		0.47	P
Vest4		0.15
MutPred		0.37		Loss of ubiquitination at K277 (P = 0.0103);
MVP		0.41
ClinPred		0.82	D
GERP RS		-0.59
Varity_R		0.17
gMVP		0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs1331341445; hg19: chr7-143881426;