6-7365869-C-A

Variant names:

• chr6-7365869-C-A
• rs1243048072
• NM_001170692.2:c.2020G>T

Variant summary

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

The NM_001170692.2(CAGE1):​c.2020G>T​(p.Asp674Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,128 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CAGE1 NM_001170692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45

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=0.19114268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAGE1	NM_001170692.2	c.2020G>T	p.Asp674Tyr	missense_variant	Exon 8 of 14	ENST00000502583.6	NP_001164163.1
CAGE1	NM_001170693.2	c.2020G>T	p.Asp674Tyr	missense_variant	Exon 8 of 13		NP_001164164.1
CAGE1	NM_205864.3	c.1597-294G>T		intron_variant	Intron 6 of 10		NP_995586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAGE1	ENST00000502583.6	c.2020G>T	p.Asp674Tyr	missense_variant	Exon 8 of 14	5	NM_001170692.2	ENSP00000425493.1
CAGE1	ENST00000338150.8	c.2020G>T	p.Asp674Tyr	missense_variant	Exon 8 of 13	2		ENSP00000338107.4
CAGE1	ENST00000379918.8	c.1954G>T	p.Asp652Tyr	missense_variant	Exon 8 of 14	5		ENSP00000369250.4
CAGE1	ENST00000512086.5	c.2005-294G>T		intron_variant	Intron 7 of 11	5		ENSP00000427583.1
CAGE1	ENST00000296742.11	c.1597-294G>T		intron_variant	Intron 6 of 10	1		ENSP00000296742.7
CAGE1	ENST00000442019.6	n.*1286G>T		non_coding_transcript_exon_variant	Exon 8 of 14	1		ENSP00000391746.2
CAGE1	ENST00000458291.6	n.2020G>T		non_coding_transcript_exon_variant	Exon 8 of 14	1		ENSP00000390644.2
CAGE1	ENST00000442019.6	n.*1286G>T		3_prime_UTR_variant	Exon 8 of 14	1		ENSP00000391746.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74318

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2020G>T (p.D674Y) alteration is located in exon 8 (coding exon 7) of the CAGE1 gene. This alteration results from a G to T substitution at nucleotide position 2020, causing the aspartic acid (D) at amino acid position 674 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
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Benign	0.078
Eigen_PC	Benign	0.058
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.99	.;.;D
Vest4		0.23
MutPred		0.31		.;Loss of disorder (P = 0.0071);Loss of disorder (P = 0.0071);
MVP		0.44
MPC		0.52
ClinPred		0.86	D
GERP RS		2.6
gMVP		0.11

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: rs1243048072; hg19: chr6-7366102;