chr22-45923037-T-C

Position:

• chr22-45923037-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_058238.3(WNT7B):​c.869A>G​(p.Gln290Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: WNT7B NM_058238.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.62

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 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=0.30944723).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT7B	NM_058238.3	c.869A>G	p.Gln290Arg	missense_variant	4/4	ENST00000339464.9
WNT7B	NM_001410806.1	c.881A>G	p.Gln294Arg	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT7B	ENST00000339464.9	c.869A>G	p.Gln290Arg	missense_variant	4/4	1	NM_058238.3	P4
WNT7B	ENST00000409496.7	c.881A>G	p.Gln294Arg	missense_variant	4/4	2		A1
WNT7B	ENST00000410089.5	c.821A>G	p.Gln274Arg	missense_variant	4/4	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.869A>G (p.Q290R) alteration is located in exon 4 (coding exon 4) of the WNT7B gene. This alteration results from a A to G substitution at nucleotide position 869, causing the glutamine (Q) at amino acid position 290 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	Benign	0.081
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Uncertain	0.60	D;.;D
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.040	N;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.13
MutPred		0.58		.;Gain of methylation at Q294 (P = 0.0157);.;
MVP		0.67
MPC		0.79
ClinPred		0.38	T
GERP RS		3.9
Varity_R		0.26
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-46318917;