Variant 6-7334072-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001170692.2(CAGE1):c.2388A>C(p.Lys796Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000579 in 1,382,108 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

CAGE1
NM_001170692.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

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

CAGE1 links:

SSR1 (HGNC:):

SSR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.27445173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAGE1	NM_001170692.2 linkuse as main transcript	c.2388A>C	p.Lys796Asn	missense_variant	12/14	ENST00000502583.6	NP_001164163.1	Q8TC20-5
CAGE1	NM_001170693.2 linkuse as main transcript	c.2283A>C	p.Lys761Asn	missense_variant	11/13		NP_001164164.1	Q8TC20-3
CAGE1	NM_205864.3 linkuse as main transcript	c.1794A>C	p.Lys598Asn	missense_variant	9/11		NP_995586.1	Q8TC20-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CAGE1	ENST00000502583.6 linkuse as main transcript	c.2388A>C	p.Lys796Asn	missense_variant	12/14	5	NM_001170692.2	ENSP00000425493.1	Q8TC20-5
CAGE1	ENST00000338150.8 linkuse as main transcript	c.2283A>C	p.Lys761Asn	missense_variant	11/13	2		ENSP00000338107.4	Q8TC20-3
CAGE1	ENST00000379918.8 linkuse as main transcript	c.2322A>C	p.Lys774Asn	missense_variant	12/14	5		ENSP00000369250.4	E7EUJ7
CAGE1	ENST00000512086.5 linkuse as main transcript	c.2202A>C	p.Lys734Asn	missense_variant	10/12	5		ENSP00000427583.1	Q8TC20-1
CAGE1	ENST00000296742.11 linkuse as main transcript	c.1794A>C	p.Lys598Asn	missense_variant	9/11	1		ENSP00000296742.7	Q8TC20-2
CAGE1	ENST00000442019.6 linkuse as main transcript	n.*1654A>C		non_coding_transcript_exon_variant	12/14	1		ENSP00000391746.2	D6R9A7
CAGE1	ENST00000458291.6 linkuse as main transcript	n.*340A>C		non_coding_transcript_exon_variant	12/14	1		ENSP00000390644.2	Q8TC20-4
CAGE1	ENST00000442019.6 linkuse as main transcript	n.*1654A>C		3_prime_UTR_variant	12/14	1		ENSP00000391746.2	D6R9A7
CAGE1	ENST00000458291.6 linkuse as main transcript	n.*340A>C		3_prime_UTR_variant	12/14	1		ENSP00000390644.2	Q8TC20-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000628

AC:

AN:

159268

Hom.:

AF XY:

0.00

AC XY:

AN XY:

84012

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000156

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000579

AC:

AN:

1382108

Hom.:

Cov.:

AF XY:

0.00000586

AC XY:

AN XY:

682986

show subpopulations

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:

9.39e-7

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.2388A>C (p.K796N) alteration is located in exon 12 (coding exon 11) of the CAGE1 gene. This alteration results from a A to C substitution at nucleotide position 2388, causing the lysine (K) at amino acid position 796 to be replaced by an asparagine (N). 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

Uncertain

0.52

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0046

.;.;.;T;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.74

T;T;T;T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.27

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

.;.;.;L;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.2

N;N;N;N;N

REVEL

Benign

0.072

Sift

Uncertain

0.0080

D;D;D;D;D

Sift4G

Benign

0.072

T;T;D;D;D

Polyphen

1.0

.;.;.;D;D

Vest4

0.23

MutPred

0.17

.;.;.;Loss of ubiquitination at K734 (P = 0.0034);.;

MVP

0.64

MPC

0.45

ClinPred

0.89

GERP RS

3.5

Varity_R

0.18

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over