rs924061115

Variant names:

• chr22-45931177-C-A
• rs924061115
• NM_058238.3:c.491G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-45931177-C-A
• chr22-45931177-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_058238.3(WNT7B):​c.491G>T​(p.Arg164Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R164Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: WNT7B NM_058238.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.79

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.951

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT7B	NM_058238.3	c.491G>T	p.Arg164Leu	missense_variant	Exon 3 of 4	ENST00000339464.9	NP_478679.1
WNT7B	NM_001410806.1	c.503G>T	p.Arg168Leu	missense_variant	Exon 3 of 4		NP_001397735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT7B	ENST00000339464.9	c.491G>T	p.Arg164Leu	missense_variant	Exon 3 of 4	1	NM_058238.3	ENSP00000341032.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447198 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 720482

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000585 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.93	D;.;D;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Pathogenic	0.29	D
MetaRNN	Pathogenic	0.95	D;D;D;D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Uncertain	2.4	M;.;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.3	D;D;D;D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.91	P;P;.;.
Vest4		0.88
MutPred		0.82		.;Loss of MoRF binding (P = 0.011);.;.;
MVP		0.95
MPC		1.6
ClinPred		0.99	D
GERP RS		2.1
Varity_R		0.71
gMVP		0.88

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

Other links and lift over

dbSNP: rs924061115; hg19: chr22-46327057;