rs2228399

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005814.3(GPA33):c.495G>T(p.Lys165Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,613,588 control chromosomes in the GnomAD database, including 110 homozygotes. 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K165E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.016 ( 58 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 52 hom. )

Consequence

GPA33
NM_005814.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.16

Publications

4 publications found

Variant links:

Genes affected

GPA33 (HGNC:4445): (glycoprotein A33) The glycoprotein encoded by this gene is a cell surface antigen that is expressed in greater than 95% of human colon cancers. The open reading frame encodes a 319-amino acid polypeptide having a putative secretory signal sequence and 3 potential glycosylation sites. The predicted mature protein has a 213-amino acid extracellular region, a single transmembrane domain, and a 62-amino acid intracellular tail. The sequence of the extracellular region contains 2 domains characteristic of the CD2 subgroup of the immunoglobulin (Ig) superfamily. [provided by RefSeq, Jul 2008]

GPA33 links:

GPA33-AS1 (HGNC:58358):

GPA33-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019969344).

BP6

Variant 1-167063658-C-A is Benign according to our data. Variant chr1-167063658-C-A is described in ClinVar as Benign. ClinVar VariationId is 772820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005814.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPA33	NM_005814.3	MANE Select	c.495G>T	p.Lys165Asn	missense	Exon 4 of 7	NP_005805.1	Q99795

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPA33	ENST00000367868.4	TSL:1 MANE Select	c.495G>T	p.Lys165Asn	missense	Exon 4 of 7	ENSP00000356842.3	Q99795
GPA33	ENST00000903072.1		c.687G>T	p.Lys229Asn	missense	Exon 6 of 9	ENSP00000573131.1
GPA33	ENST00000903065.1		c.681G>T	p.Lys227Asn	missense	Exon 5 of 8	ENSP00000573124.1

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2371

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0535

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00753

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.0163

GnomAD2 exomes

AF:

0.00393

AC:

988

AN:

251406

AF XY:

0.00266

show subpopulations

Gnomad AFR exome

AF:

0.0541

Gnomad AMR exome

AF:

0.00258

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00148

AC:

2168

AN:

1461318

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

941

AN XY:

726956

show subpopulations

African (AFR)

AF:

0.0537

AC:

1797

AN:

33458

American (AMR)

AF:

0.00311

AC:

139

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00255

AC:

AN:

5494

European-Non Finnish (NFE)

AF:

0.0000405

AC:

AN:

1111814

Other (OTH)

AF:

0.00282

AC:

170

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

101

202

302

403

504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0156

AC:

2370

AN:

152270

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1118

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0533

AC:

2215

AN:

41532

American (AMR)

AF:

0.00752

AC:

115

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68022

Other (OTH)

AF:

0.0161

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

111

222

332

443

554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00577

Hom.:

Bravo

AF:

0.0179

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0565

AC:

249

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00509

AC:

618

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0055

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.2

PhyloP100

-1.2

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.7

REVEL

Benign

0.092

Sift

Benign

0.27

Sift4G

Benign

0.46

Polyphen

0.55

Vest4

0.11

MutPred

0.12

Loss of ubiquitination at K165 (P = 0.0071)

MVP

0.31

MPC

0.19

ClinPred

0.0089

GERP RS

0.73

Varity_R

0.081

gMVP

0.50

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over