chr12-130163504-G-T

Position:

• chr12-130163504-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007197.4(FZD10):​c.562G>T​(p.Gly188Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FZD10 NM_007197.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FZD10	NM_007197.4	c.562G>T	p.Gly188Trp	missense_variant	1/1	ENST00000229030.5	NP_009128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FZD10	ENST00000229030.5	c.562G>T	p.Gly188Trp	missense_variant	1/1	6	NM_007197.4	ENSP00000229030.4
FZD10	ENST00000539839.1	c.464G>T	p.Arg155Leu	missense_variant	1/1	6		ENSP00000438460.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1432338 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 710022

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Apr 01, 2024

The c.562G>T (p.G188W) alteration is located in exon 1 (coding exon 1) of the FZD10 gene. This alteration results from a G to T substitution at nucleotide position 562, causing the glycine (G) at amino acid position 188 to be replaced by a tryptophan (W). 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	0.13
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	23
DANN	Benign	0.90
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.36
Sift	Benign	0.11	T
Sift4G	Uncertain	0.022	D
Polyphen		0.98	D
Vest4		0.21
MutPred		0.36		Loss of disorder (P = 0.1216);
MVP		0.59
ClinPred		0.72	D
GERP RS		4.9
Varity_R		0.091
gMVP		0.54

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: chr12-130648049;