rs767074475

Variant names:

• chr1-167055070-C-A
• rs767074475
• NM_005814.3:c.733G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-167055070-C-A
• chr1-167055070-C-G
• chr1-167055070-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005814.3(GPA33):​c.733G>T​(p.Val245Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V245M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPA33 NM_005814.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• Publications: 0 publications found

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]

ENSG00000227907 (HGNC:58358):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07914302).

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.733G>T	p.Val245Leu	missense	Exon 6 of 7	NP_005805.1	Q99795

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPA33	ENST00000367868.4	TSL:1 MANE Select	c.733G>T	p.Val245Leu	missense	Exon 6 of 7	ENSP00000356842.3	Q99795
	GPA33	ENST00000903072.1		c.925G>T	p.Val309Leu	missense	Exon 8 of 9	ENSP00000573131.1
	GPA33	ENST00000903065.1		c.919G>T	p.Val307Leu	missense	Exon 7 of 8	ENSP00000573124.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.5
DANN	Benign	0.85
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.095
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.0070
Sift	Benign	0.31	T
Sift4G	Benign	0.23	T
Polyphen		0.012	B
Vest4		0.17
MutPred		0.47		Loss of sheet (P = 0.1158)
MVP		0.38
MPC		0.069
ClinPred		0.074	T
GERP RS		1.6
Varity_R		0.059
gMVP		0.41
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs767074475; hg19: chr1-167024307;