rs765524304

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007197.4(FZD10):​c.542C>A​(p.Pro181Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. P181R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FZD10
NM_007197.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.362
Variant links:
Genes affected
FZD10 (HGNC:4039): (frizzled class receptor 10) This gene is a member of the frizzled gene family. Members of this family encode 7-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. Using array analysis, expression of this intronless gene is significantly up-regulated in two cases of primary colon cancer. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.060170233).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FZD10NM_007197.4 linkc.542C>A p.Pro181Gln missense_variant Exon 1 of 1 ENST00000229030.5 NP_009128.1 Q9ULW2Q6NSL8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FZD10ENST00000229030.5 linkc.542C>A p.Pro181Gln missense_variant Exon 1 of 1 6 NM_007197.4 ENSP00000229030.4 Q9ULW2
FZD10ENST00000539839.1 linkc.444C>A p.Pro148Pro synonymous_variant Exon 1 of 1 6 ENSP00000438460.1 F5H450

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1448738
Hom.:
0
Cov.:
34
AF XY:
0.00000139
AC XY:
1
AN XY:
719624
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
9.4
DANN
Benign
0.92
DEOGEN2
Benign
0.35
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.060
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
-0.34
N
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.80
N
REVEL
Benign
0.15
Sift
Benign
0.083
T
Sift4G
Benign
0.20
T
Polyphen
0.0
B
Vest4
0.055
MutPred
0.20
Loss of glycosylation at P181 (P = 0.0988);
MVP
0.061
ClinPred
0.076
T
GERP RS
-8.3
Varity_R
0.038
gMVP
0.44

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: rs765524304; hg19: chr12-130648029; API