6-7373296-C-A

Position:

• chr6-7373296-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001170692.2(CAGE1):​c.1523G>T​(p.Arg508Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CAGE1 NM_001170692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.147

Genes affected

CAGE1 (HGNC:21622): (cancer antigen 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23863944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAGE1	NM_001170692.2	c.1523G>T	p.Arg508Ile	missense_variant	5/14	ENST00000502583.6	NP_001164163.1
CAGE1	NM_001170693.2	c.1523G>T	p.Arg508Ile	missense_variant	5/13		NP_001164164.1
CAGE1	NM_205864.3	c.1115G>T	p.Arg372Ile	missense_variant	4/11		NP_995586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAGE1	ENST00000502583.6	c.1523G>T	p.Arg508Ile	missense_variant	5/14	5	NM_001170692.2	ENSP00000425493.1
CAGE1	ENST00000338150.8	c.1523G>T	p.Arg508Ile	missense_variant	5/13	2		ENSP00000338107.4
CAGE1	ENST00000379918.8	c.1523G>T	p.Arg508Ile	missense_variant	5/14	5		ENSP00000369250.4
CAGE1	ENST00000512086.5	c.1523G>T	p.Arg508Ile	missense_variant	5/12	5		ENSP00000427583.1
CAGE1	ENST00000296742.11	c.1115G>T	p.Arg372Ile	missense_variant	4/11	1		ENSP00000296742.7
CAGE1	ENST00000512691.1	c.1559G>T	p.Arg520Ile	missense_variant	5/5	5		ENSP00000423789.1
CAGE1	ENST00000442019.6	n.*789G>T		non_coding_transcript_exon_variant	5/14	1		ENSP00000391746.2
CAGE1	ENST00000458291.6	n.1523G>T		non_coding_transcript_exon_variant	5/14	1		ENSP00000390644.2
CAGE1	ENST00000442019.6	n.*789G>T		3_prime_UTR_variant	5/14	1		ENSP00000391746.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453258 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 722454

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Sep 03, 2024

The c.1523G>T (p.R508I) alteration is located in exon 5 (coding exon 4) of the CAGE1 gene. This alteration results from a G to T substitution at nucleotide position 1523, causing the arginine (R) at amino acid position 508 to be replaced by an isoleucine (I). 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	0.19
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.024	.;.;.;T;.;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.090	N
LIST_S2	Uncertain	0.88	D;D;D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.24	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;L;.;L;L;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D;D
REVEL	Benign	0.063
Sift	Uncertain	0.014	D;D;D;D;D;D
Sift4G	Uncertain	0.042	D;T;T;T;T;T
Polyphen		0.98, 0.83	.;.;.;D;P;.
Vest4		0.39
MutPred		0.41		Loss of MoRF binding (P = 0.0342);Loss of MoRF binding (P = 0.0342);.;Loss of MoRF binding (P = 0.0342);Loss of MoRF binding (P = 0.0342);.;
MVP		0.66
MPC		0.61
ClinPred		0.93	D
GERP RS		3.6
Varity_R		0.13
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-7373529;