1-167063590-G-A

Position:

• chr1-167063590-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005814.3(GPA33):​c.563C>T​(p.Ala188Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPA33 NM_005814.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.124

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]

LOC105371600 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03771922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPA33	NM_005814.3	c.563C>T	p.Ala188Val	missense_variant	4/7	ENST00000367868.4	NP_005805.1
GPA33	XM_017000005.2	c.239C>T	p.Ala80Val	missense_variant	5/8		XP_016855494.1
GPA33	XM_047424480.1	c.239C>T	p.Ala80Val	missense_variant	6/9		XP_047280436.1
LOC105371600	XR_922249.3	n.545+473G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPA33	ENST00000367868.4	c.563C>T	p.Ala188Val	missense_variant	4/7	1	NM_005814.3	ENSP00000356842.3
GPA33	ENST00000527955.5	n.654C>T		non_coding_transcript_exon_variant	4/7	5
GPA33	ENST00000632571.1	c.*40C>T		downstream_gene_variant		4		ENSP00000488407.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 04, 2024

The c.563C>T (p.A188V) alteration is located in exon 4 (coding exon 4) of the GPA33 gene. This alteration results from a C to T substitution at nucleotide position 563, causing the alanine (A) at amino acid position 188 to be replaced by a valine (V). 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	0.083
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.3
DANN	Benign	0.93
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.56	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.039
Sift	Benign	0.23	T
Sift4G	Benign	0.21	T
Polyphen		0.051	B
Vest4		0.070
MutPred		0.22		Loss of glycosylation at P186 (P = 0.0919);
MVP		0.17
MPC		0.068
ClinPred		0.056	T
GERP RS		0.16
Varity_R		0.065
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-167032827;