Variant 6-7365478-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001170692.2(CAGE1):c.2183T>C(p.Leu728Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CAGE1
NM_001170692.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.85

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAGE1	NM_001170692.2 linkuse as main transcript	c.2183T>C	p.Leu728Pro	missense_variant	9/14	ENST00000502583.6	NP_001164163.1	Q8TC20-5
CAGE1	NM_001170693.2 linkuse as main transcript	c.2183T>C	p.Leu728Pro	missense_variant	9/13		NP_001164164.1	Q8TC20-3
CAGE1	NM_205864.3 linkuse as main transcript	c.1694T>C	p.Leu565Pro	missense_variant	7/11		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.2183T>C	p.Leu728Pro	missense_variant	9/14	5	NM_001170692.2	ENSP00000425493.1	Q8TC20-5
CAGE1	ENST00000338150.8 linkuse as main transcript	c.2183T>C	p.Leu728Pro	missense_variant	9/13	2		ENSP00000338107.4	Q8TC20-3
CAGE1	ENST00000379918.8 linkuse as main transcript	c.2117T>C	p.Leu706Pro	missense_variant	9/14	5		ENSP00000369250.4	E7EUJ7
CAGE1	ENST00000512086.5 linkuse as main transcript	c.2102T>C	p.Leu701Pro	missense_variant	8/12	5		ENSP00000427583.1	Q8TC20-1
CAGE1	ENST00000296742.11 linkuse as main transcript	c.1694T>C	p.Leu565Pro	missense_variant	7/11	1		ENSP00000296742.7	Q8TC20-2
CAGE1	ENST00000442019.6 linkuse as main transcript	n.*1449T>C		non_coding_transcript_exon_variant	9/14	1		ENSP00000391746.2	D6R9A7
CAGE1	ENST00000458291.6 linkuse as main transcript	n.*135T>C		non_coding_transcript_exon_variant	9/14	1		ENSP00000390644.2	Q8TC20-4
CAGE1	ENST00000442019.6 linkuse as main transcript	n.*1449T>C		3_prime_UTR_variant	9/14	1		ENSP00000391746.2	D6R9A7
CAGE1	ENST00000458291.6 linkuse as main transcript	n.*135T>C		3_prime_UTR_variant	9/14	1		ENSP00000390644.2	Q8TC20-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000807

AC:

AN:

247866

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134424

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460388

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726446

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

AC:

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

Jul 20, 2021

The c.2183T>C (p.L728P) alteration is located in exon 9 (coding exon 8) of the CAGE1 gene. This alteration results from a T to C substitution at nucleotide position 2183, causing the leucine (L) at amino acid position 728 to be replaced by a proline (P). 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

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

.;.;.;T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.68

T;T;T;T;T

M_CAP

Benign

0.048

MetaRNN

Pathogenic

0.76

D;D;D;D;D

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.3

.;.;.;M;.

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-4.9

D;D;D;D;D

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Uncertain

0.055

T;D;D;D;D

Polyphen

1.0

.;.;.;D;D

Vest4

0.91

MutPred

0.58

.;.;.;Loss of stability (P = 0.0131);.;

MVP

0.81

MPC

0.59

ClinPred

0.99

GERP RS

5.5

Varity_R

0.89

gMVP

0.58

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