12-130163003-A-G

Position:

• chr12-130163003-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007197.4(FZD10):​c.61A>G​(p.Ile21Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,444,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FZD10 NM_007197.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.48

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1541504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FZD10	NM_007197.4	c.61A>G	p.Ile21Val	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.61A>G	p.Ile21Val	missense_variant	1/1	6	NM_007197.4	ENSP00000229030.4
FZD10	ENST00000539839.1	c.-38A>G		5_prime_UTR_variant	1/1	6		ENSP00000438460.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444772 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 717248

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: 0.0000168

GnomAD4 genome Cov.: 32

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

Oct 16, 2024

The c.61A>G (p.I21V) alteration is located in exon 1 (coding exon 1) of the FZD10 gene. This alteration results from a A to G substitution at nucleotide position 61, causing the isoleucine (I) at amino acid position 21 to be replaced by a valine (V). 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	0.095
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.97
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.053
Eigen_PC	Benign	0.039
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.080	N
REVEL	Benign	0.22
Sift	Benign	0.20	T
Sift4G	Benign	0.70	T
Polyphen		0.38	B
Vest4		0.31
MutPred		0.34		Gain of catalytic residue at I21 (P = 0.0676);
MVP		0.076
ClinPred		0.37	T
GERP RS		3.4
Varity_R		0.063
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-130647548;