Variant 1-167054353-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005814.3(GPA33):c.941C>T(p.Pro314Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,613,998 control chromosomes in the GnomAD database, including 2 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00099 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

GPA33
NM_005814.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.136

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:

ENSG00000227907 (HGNC:):

ENSG00000227907 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049874783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPA33	NM_005814.3 link	c.941C>T	p.Pro314Leu	missense_variant	7/7	ENST00000367868.4	NP_005805.1	Q99795
GPA33	XM_017000005.2 link	c.617C>T	p.Pro206Leu	missense_variant	8/8		XP_016855494.1
GPA33	XM_047424480.1 link	c.617C>T	p.Pro206Leu	missense_variant	9/9		XP_047280436.1
LOC105371600	XR_922249.3 link	n.82+1587G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GPA33	ENST00000367868.4 link	c.941C>T	p.Pro314Leu	missense_variant	7/7	1	NM_005814.3	ENSP00000356842.3	Q99795
GPA33	ENST00000527955.5 link	n.1032C>T		non_coding_transcript_exon_variant	7/7	5
ENSG00000227907	ENST00000417644.1 link	n.216+1587G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000934

AC:

142

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00287

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000344

AC:

AN:

250080

Hom.:

AF XY:

0.000244

AC XY:

AN XY:

135322

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000122

AC:

178

AN:

1461772

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00221

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000985

AC:

150

AN:

152226

Hom.:

Cov.:

AF XY:

0.000954

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00306

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000548

Hom.:

Bravo

AF:

0.00109

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000346

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Mar 28, 2024

The c.941C>T (p.P314L) alteration is located in exon 7 (coding exon 7) of the GPA33 gene. This alteration results from a C to T substitution at nucleotide position 941, causing the proline (P) at amino acid position 314 to be replaced by a leucine (L). 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

0.097

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.081

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.56

M_CAP

Benign

0.081

MetaRNN

Benign

0.0050

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.7

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.090

Sift

Uncertain

0.012

Sift4G

Uncertain

0.029

Polyphen

0.027

Vest4

0.054

MVP

0.78

MPC

0.16

ClinPred

0.027

GERP RS

0.90

Varity_R

0.056

gMVP

0.26

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