Variant 1-167063674-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_005814.3(GPA33):c.479T>C(p.Leu160Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,452 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: 0.0000021 ( 0 hom. )

Consequence

GPA33
NM_005814.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94

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:

LOC105371600 (HGNC:):

LOC105371600 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.962

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPA33	NM_005814.3 link	c.479T>C	p.Leu160Pro	missense_variant	4/7	ENST00000367868.4	NP_005805.1	Q99795
GPA33	XM_017000005.2 link	c.155T>C	p.Leu52Pro	missense_variant	5/8		XP_016855494.1
GPA33	XM_047424480.1 link	c.155T>C	p.Leu52Pro	missense_variant	6/9		XP_047280436.1
LOC105371600	XR_922249.3 link	n.545+557A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GPA33	ENST00000367868.4 link	c.479T>C	p.Leu160Pro	missense_variant	4/7	1	NM_005814.3	ENSP00000356842.3	Q99795
GPA33	ENST00000632571.1 link	c.155T>C	p.Leu52Pro	missense_variant	4/4	4		ENSP00000488407.1	A0A0J9YXH7
GPA33	ENST00000527955.5 link	n.570T>C		non_coding_transcript_exon_variant	4/7	5
GPA33	ENST00000534512.1 link	n.*300T>C		downstream_gene_variant		4		ENSP00000431195.1	E9PMB2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251416

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461452

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Jan 11, 2023

The c.479T>C (p.L160P) alteration is located in exon 4 (coding exon 4) of the GPA33 gene. This alteration results from a T to C substitution at nucleotide position 479, causing the leucine (L) at amino acid position 160 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

0.98

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.42

T;D

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.68

T;T

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Uncertain

-0.076

MutationAssessor

Pathogenic

4.4

H;.

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-5.8

D;.

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.0030

D;.

Polyphen

1.0

D;.

Vest4

0.95

MutPred

0.81

Gain of disorder (P = 0.0057);.;

MVP

0.75

MPC

0.51

ClinPred

1.0

GERP RS

5.6

Varity_R

0.99

gMVP

0.98

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