chr6-7373173-T-C

Position:

chr6-7373173-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001170692.2(CAGE1):c.1646A>G(p.Gln549Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,613,842 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

CAGE1
NM_001170692.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

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

CAGE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07731786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAGE1	NM_001170692.2 linkuse as main transcript	c.1646A>G	p.Gln549Arg	missense_variant	5/14	ENST00000502583.6	NP_001164163.1	Q8TC20-5
CAGE1	NM_001170693.2 linkuse as main transcript	c.1646A>G	p.Gln549Arg	missense_variant	5/13		NP_001164164.1	Q8TC20-3
CAGE1	NM_205864.3 linkuse as main transcript	c.1238A>G	p.Gln413Arg	missense_variant	4/11		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.1646A>G	p.Gln549Arg	missense_variant	5/14	5	NM_001170692.2	ENSP00000425493.1	Q8TC20-5
CAGE1	ENST00000338150.8 linkuse as main transcript	c.1646A>G	p.Gln549Arg	missense_variant	5/13	2		ENSP00000338107.4	Q8TC20-3
CAGE1	ENST00000379918.8 linkuse as main transcript	c.1646A>G	p.Gln549Arg	missense_variant	5/14	5		ENSP00000369250.4	E7EUJ7
CAGE1	ENST00000512086.5 linkuse as main transcript	c.1646A>G	p.Gln549Arg	missense_variant	5/12	5		ENSP00000427583.1	Q8TC20-1
CAGE1	ENST00000296742.11 linkuse as main transcript	c.1238A>G	p.Gln413Arg	missense_variant	4/11	1		ENSP00000296742.7	Q8TC20-2
CAGE1	ENST00000442019.6 linkuse as main transcript	n.*912A>G		non_coding_transcript_exon_variant	5/14	1		ENSP00000391746.2	D6R9A7
CAGE1	ENST00000458291.6 linkuse as main transcript	n.1646A>G		non_coding_transcript_exon_variant	5/14	1		ENSP00000390644.2	Q8TC20-4
CAGE1	ENST00000442019.6 linkuse as main transcript	n.*912A>G		3_prime_UTR_variant	5/14	1		ENSP00000391746.2	D6R9A7
CAGE1	ENST00000512691.1 linkuse as main transcript	c.*8A>G		downstream_gene_variant		5		ENSP00000423789.1	D6RCC6

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000145

AC:

AN:

248678

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

134922

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000829

GnomAD4 exome

AF:

0.0000814

AC:

119

AN:

1461500

Hom.:

Cov.:

AF XY:

0.0000922

AC XY:

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000495

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000158

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000288

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000114

Hom.:

Bravo

AF:

0.000106

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000543

AC:

ESP6500EA

AF:

0.000245

AC:

ExAC

AF:

0.000174

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000297

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 21, 2023

The c.1646A>G (p.Q549R) alteration is located in exon 5 (coding exon 4) of the CAGE1 gene. This alteration results from a A to G substitution at nucleotide position 1646, causing the glutamine (Q) at amino acid position 549 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.071

.;.;.;T;.

Eigen

Benign

-0.013

Eigen_PC

Benign

-0.090

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.56

T;T;T;T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.077

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

.;M;.;M;M

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.7

D;N;D;D;D

REVEL

Benign

0.082

Sift

Uncertain

0.0050

D;D;D;D;D

Sift4G

Benign

0.20

T;D;T;D;D

Polyphen

0.96, 0.87

.;.;.;D;P

Vest4

0.38

MVP

0.64

MPC

0.43

ClinPred

0.059

GERP RS

4.2

Varity_R

0.17

gMVP

0.083

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

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