15-55546925-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001367806.1(PYGO1):​c.358G>C​(p.Gly120Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PYGO1
NM_001367806.1 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13642314).
BS2
High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PYGO1NM_001367806.1 linkc.358G>C p.Gly120Arg missense_variant Exon 3 of 3 ENST00000563719.4 NP_001354735.1
PYGO1NM_001330326.2 linkc.358G>C p.Gly120Arg missense_variant Exon 3 of 4 NP_001317255.1 Q9Y3Y4-2
PYGO1NM_015617.3 linkc.358G>C p.Gly120Arg missense_variant Exon 3 of 3 NP_056432.1 Q9Y3Y4-1
PYGO1XM_047432381.1 linkc.43G>C p.Gly15Arg missense_variant Exon 3 of 3 XP_047288337.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PYGO1ENST00000563719.4 linkc.358G>C p.Gly120Arg missense_variant Exon 3 of 3 5 NM_001367806.1 ENSP00000457777.1 Q9Y3Y4-2
PYGO1ENST00000302000.10 linkc.358G>C p.Gly120Arg missense_variant Exon 3 of 3 1 ENSP00000302327.6 Q9Y3Y4-1
PYGO1ENST00000645724.1 linkc.358G>C p.Gly120Arg missense_variant Exon 3 of 4 ENSP00000496139.1 Q9Y3Y4-2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152068
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251264
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135784
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000261
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461850
Hom.:
0
Cov.:
31
AF XY:
0.0000151
AC XY:
11
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.358G>C (p.G120R) alteration is located in exon 3 (coding exon 3) of the PYGO1 gene. This alteration results from a G to C substitution at nucleotide position 358, causing the glycine (G) at amino acid position 120 to be replaced by an arginine (R). 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
Pathogenic
0.76
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T;.;.
Eigen
Benign
-0.019
Eigen_PC
Benign
0.086
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.89
D;.;D
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.0
M;M;M
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-3.1
D;.;D
REVEL
Benign
0.16
Sift
Uncertain
0.0010
D;.;D
Sift4G
Uncertain
0.010
D;.;D
Polyphen
0.62
P;.;.
Vest4
0.70
MutPred
0.43
Gain of solvent accessibility (P = 0.0171);Gain of solvent accessibility (P = 0.0171);Gain of solvent accessibility (P = 0.0171);
MVP
0.56
MPC
0.40
ClinPred
0.41
T
GERP RS
4.2
Varity_R
0.29
gMVP
0.66

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.

Other links and lift over

dbSNP: rs563762840; hg19: chr15-55839123; API