NM_138300.4:c.503A>C

Variant names:

• chr1-154959497-T-G
• rs145705800
• NM_138300.4:c.503A>C

Variant summary

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

The NM_138300.4(PYGO2):​c.503A>C​(p.Asn168Thr) 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. N168S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PYGO2 NM_138300.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749
• Publications: 1 publications found

Genes affected

PYGO2 (HGNC:30257): (pygopus family PHD finger 2) Predicted to enable several functions, including chromatin binding activity; histone acetyltransferase regulator activity; and histone binding activity. Predicted to be involved in kidney development and spermatid nucleus differentiation. Predicted to act upstream of or within several processes, including animal organ development; positive regulation of chromatin binding activity; and regulation of histone H3-K4 methylation. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000310191 (HGNC:):

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=0.09787795).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138300.4. 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
	PYGO2	NM_138300.4	MANE Select	c.503A>C	p.Asn168Thr	missense	Exon 3 of 3	NP_612157.1	Q9BRQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYGO2	ENST00000368457.3	TSL:1 MANE Select	c.503A>C	p.Asn168Thr	missense	Exon 3 of 3	ENSP00000357442.2	Q9BRQ0
	PYGO2	ENST00000368456.1	TSL:2	c.392A>C	p.Asn131Thr	missense	Exon 3 of 3	ENSP00000357441.1	Q5T171
	ENSG00000310191	ENST00000848032.1		n.424-1384T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	-0.61
CADD	Benign	9.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.75
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.059
Sift	Uncertain	0.010	D
Sift4G	Benign	0.13	T
Polyphen		0.012	B
Vest4		0.27
MutPred		0.10		Gain of phosphorylation at N168 (P = 0.0247)
MVP		0.36
MPC		0.23
ClinPred		0.066	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.099
gMVP		0.10
Mutation Taster		=57/43	polymorphism

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

Other links and lift over

dbSNP: rs145705800; hg19: chr1-154931973;