6-7369980-G-T

Position:

• chr6-7369980-G-T

Variant summary

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

The NM_001170692.2(CAGE1):​c.1832C>A​(p.Ser611Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAGE1 NM_001170692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30

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=0.31142217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAGE1	NM_001170692.2	c.1832C>A	p.Ser611Tyr	missense_variant	6/14	ENST00000502583.6	NP_001164163.1
CAGE1	NM_001170693.2	c.1832C>A	p.Ser611Tyr	missense_variant	6/13		NP_001164164.1
CAGE1	NM_205864.3	c.1424C>A	p.Ser475Tyr	missense_variant	5/11		NP_995586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAGE1	ENST00000502583.6	c.1832C>A	p.Ser611Tyr	missense_variant	6/14	5	NM_001170692.2	ENSP00000425493.1
CAGE1	ENST00000338150.8	c.1832C>A	p.Ser611Tyr	missense_variant	6/13	2		ENSP00000338107.4
CAGE1	ENST00000379918.8	c.1832C>A	p.Ser611Tyr	missense_variant	6/14	5		ENSP00000369250.4
CAGE1	ENST00000512086.5	c.1832C>A	p.Ser611Tyr	missense_variant	6/12	5		ENSP00000427583.1
CAGE1	ENST00000296742.11	c.1424C>A	p.Ser475Tyr	missense_variant	5/11	1		ENSP00000296742.7
CAGE1	ENST00000442019.6	n.*1098C>A		non_coding_transcript_exon_variant	6/14	1		ENSP00000391746.2
CAGE1	ENST00000458291.6	n.1832C>A		non_coding_transcript_exon_variant	6/14	1		ENSP00000390644.2
CAGE1	ENST00000442019.6	n.*1098C>A		3_prime_UTR_variant	6/14	1		ENSP00000391746.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Feb 22, 2023

The c.1832C>A (p.S611Y) alteration is located in exon 6 (coding exon 5) of the CAGE1 gene. This alteration results from a C to A substitution at nucleotide position 1832, causing the serine (S) at amino acid position 611 to be replaced by a tyrosine (Y). 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	0.17
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	.;.;.;T;.
Eigen	Benign	-0.020
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.77	T;T;T;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.31	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;M;.;M;M
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.2	D;D;D;D;D
REVEL	Benign	0.062
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D
Polyphen		0.90, 1.0	.;.;.;P;D
Vest4		0.52
MutPred		0.23		Loss of disorder (P = 0.0085);Loss of disorder (P = 0.0085);.;Loss of disorder (P = 0.0085);Loss of disorder (P = 0.0085);
MVP		0.54
MPC		0.52
ClinPred		0.95	D
GERP RS		3.4
Varity_R		0.29
gMVP		0.22

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: rs1760485882; hg19: chr6-7370213;