chr15-55546723-A-C

Variant names:

• chr15-55546723-A-C
• NM_001367806.1:c.560T>G

Variant summary

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

The NM_001367806.1(PYGO1):​c.560T>G​(p.Ile187Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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: PYGO1 NM_001367806.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.10
• Publications: 0 publications found

Genes affected

PYGO1 (HGNC:30256): (pygopus family PHD finger 1) Enables methylated histone binding activity. Predicted to be involved in kidney development and spermatid nucleus differentiation. Predicted to act upstream of or within several processes, including hematopoietic progenitor cell differentiation; protein localization to nucleus; and spermatid development. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2095612).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367806.1. 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
	PYGO1	NM_001367806.1	MANE Select	c.560T>G	p.Ile187Ser	missense	Exon 3 of 3	NP_001354735.1	Q9Y3Y4-2
	PYGO1	NM_001330326.2		c.560T>G	p.Ile187Ser	missense	Exon 3 of 4	NP_001317255.1	Q9Y3Y4-2
	PYGO1	NM_015617.3		c.560T>G	p.Ile187Ser	missense	Exon 3 of 3	NP_056432.1	Q9Y3Y4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYGO1	ENST00000563719.4	TSL:5 MANE Select	c.560T>G	p.Ile187Ser	missense	Exon 3 of 3	ENSP00000457777.1	Q9Y3Y4-2
	PYGO1	ENST00000302000.10	TSL:1	c.560T>G	p.Ile187Ser	missense	Exon 3 of 3	ENSP00000302327.6	Q9Y3Y4-1
	PYGO1	ENST00000645724.1		c.560T>G	p.Ile187Ser	missense	Exon 3 of 4	ENSP00000496139.1	Q9Y3Y4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.0098
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		6.1
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.36	T
Polyphen		0.079	B
Vest4		0.60
MutPred		0.25		Gain of glycosylation at I187 (P = 0.0209)
MVP		0.25
MPC		0.26
ClinPred		0.91	D
GERP RS		5.0
Varity_R		0.33
gMVP		0.69

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

hg19: chr15-55838921;