6-7355101-T-C

Position:

• chr6-7355101-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001170692.2(CAGE1):​c.2309A>G​(p.Tyr770Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CAGE1 NM_001170692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36583835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAGE1	NM_001170692.2	c.2309A>G	p.Tyr770Cys	missense_variant	11/14	ENST00000502583.6	NP_001164163.1
CAGE1	NM_001170693.2	c.2204A>G	p.Tyr735Cys	missense_variant	10/13		NP_001164164.1
CAGE1	NM_205864.3	c.1715A>G	p.Tyr572Cys	missense_variant	8/11		NP_995586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAGE1	ENST00000502583.6	c.2309A>G	p.Tyr770Cys	missense_variant	11/14	5	NM_001170692.2	ENSP00000425493.1
CAGE1	ENST00000338150.8	c.2204A>G	p.Tyr735Cys	missense_variant	10/13	2		ENSP00000338107.4
CAGE1	ENST00000379918.8	c.2243A>G	p.Tyr748Cys	missense_variant	11/14	5		ENSP00000369250.4
CAGE1	ENST00000512086.5	c.2123A>G	p.Tyr708Cys	missense_variant	9/12	5		ENSP00000427583.1
CAGE1	ENST00000296742.11	c.1715A>G	p.Tyr572Cys	missense_variant	8/11	1		ENSP00000296742.7
CAGE1	ENST00000442019.6	n.*1575A>G		non_coding_transcript_exon_variant	11/14	1		ENSP00000391746.2
CAGE1	ENST00000458291.6	n.*261A>G		non_coding_transcript_exon_variant	11/14	1		ENSP00000390644.2
CAGE1	ENST00000442019.6	n.*1575A>G		3_prime_UTR_variant	11/14	1		ENSP00000391746.2
CAGE1	ENST00000458291.6	n.*261A>G		3_prime_UTR_variant	11/14	1		ENSP00000390644.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453600 Hom.: 0 Cov.: 28 AF XY: 0.00000277 AC XY: 2 AN XY: 722960

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: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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 31, 2023

The c.2309A>G (p.Y770C) alteration is located in exon 11 (coding exon 10) of the CAGE1 gene. This alteration results from a A to G substitution at nucleotide position 2309, causing the tyrosine (Y) at amino acid position 770 to be replaced by a cysteine (C). 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	0.20
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	.;.;.;T;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.75	T;T;T;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.37	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	.;.;.;M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D
REVEL	Benign	0.27
Sift	Benign	0.058	T;T;T;T;T
Sift4G	Uncertain	0.012	D;D;T;D;D
Polyphen		1.0, 0.92	.;.;.;D;P
Vest4		0.50
MutPred		0.53		.;.;.;Gain of catalytic residue at E710 (P = 0.1784);.;
MVP		0.61
MPC		0.50
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.16
gMVP		0.29

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: chr6-7355334;