rs748420070

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_058238.3(WNT7B):​c.773G>C​(p.Arg258Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R258H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

WNT7B
NM_058238.3 missense

Scores

8
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.176
Variant links:
Genes affected
WNT7B (HGNC:12787): (Wnt family member 7B) This gene is a member of the WNT gene family, which consists of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. Among members of the human WNT family, this gene product is most similar to WNT7A protein. [provided by RefSeq, Oct 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34013242).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WNT7BNM_058238.3 linkc.773G>C p.Arg258Pro missense_variant Exon 4 of 4 ENST00000339464.9 NP_478679.1 P56706
WNT7BNM_001410806.1 linkc.785G>C p.Arg262Pro missense_variant Exon 4 of 4 NP_001397735.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WNT7BENST00000339464.9 linkc.773G>C p.Arg258Pro missense_variant Exon 4 of 4 1 NM_058238.3 ENSP00000341032.4 P56706
WNT7BENST00000409496.7 linkc.785G>C p.Arg262Pro missense_variant Exon 4 of 4 2 ENSP00000386546.3 A8K0G1
WNT7BENST00000410089.5 linkc.725G>C p.Arg242Pro missense_variant Exon 4 of 4 5 ENSP00000386781.1 B8A595

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251028
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135840
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461282
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726980
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
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
0.17
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.78
D;.;D
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.15
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.87
D;D;D
M_CAP
Uncertain
0.16
D
MetaRNN
Benign
0.34
T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
0.17
N;.;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-3.9
D;D;D
REVEL
Uncertain
0.37
Sift
Benign
0.065
T;T;T
Sift4G
Benign
0.15
T;T;T
Polyphen
0.48
P;P;.
Vest4
0.32
MutPred
0.50
.;Loss of MoRF binding (P = 0.0045);.;
MVP
0.82
MPC
1.8
ClinPred
0.82
D
GERP RS
2.9
Varity_R
0.77
gMVP
0.63

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: rs748420070; hg19: chr22-46319013; API