chr12-130163445-T-C

Variant names:

• chr12-130163445-T-C
• NM_007197.4:c.503T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007197.4(FZD10):​c.503T>C​(p.Leu168Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FZD10 NM_007197.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60
• Publications: 0 publications found

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]

FZD10-AS1 (HGNC:48632): (FZD10 antisense divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15894902).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007197.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD10	NM_007197.4	MANE Select	c.503T>C	p.Leu168Pro	missense	Exon 1 of 1	NP_009128.1	Q9ULW2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD10	ENST00000229030.5	TSL:6 MANE Select	c.503T>C	p.Leu168Pro	missense	Exon 1 of 1	ENSP00000229030.4	Q9ULW2
	FZD10	ENST00000539839.1	TSL:6	c.405T>C	p.Ala135Ala	synonymous	Exon 1 of 1	ENSP00000438460.1	F5H450
	FZD10-AS1	ENST00000815564.1		n.51A>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.84
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.64	T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.6
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.19
Sift	Benign	0.40	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.25
MutPred		0.23		Gain of glycosylation at L168 (P = 0.0567)
MVP		0.46
ClinPred		0.31	T
GERP RS		3.9
Varity_R		0.26
gMVP		0.65
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

hg19: chr12-130647990;