NM_007197.4:c.459C>T

Variant names:

• chr12-130163401-C-T
• rs766910008
• NM_007197.4:c.459C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_007197.4(FZD10):​c.459C>T​(p.Asn153Asn) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FZD10 NM_007197.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• 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=0.26718256).
• BP7: Synonymous conserved (PhyloP=1.54 with no splicing effect.

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.459C>T	p.Asn153Asn	synonymous	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.459C>T	p.Asn153Asn	synonymous	Exon 1 of 1	ENSP00000229030.4	Q9ULW2
	FZD10	ENST00000539839.1	TSL:6	c.361C>T	p.Arg121Trp	missense	Exon 1 of 1	ENSP00000438460.1	F5H450
	FZD10-AS1	ENST00000815564.1		n.95G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.97
Eigen	Benign	0.17
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.53	T
PhyloP100		1.5
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.24
Sift4G	Uncertain	0.019	D
Vest4		0.33
MutPred		0.26		Gain of catalytic residue at R124 (P = 0.0016)
MVP		0.60
ClinPred		0.43	T
GERP RS		4.1
Mutation Taster		=64/36	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

dbSNP: rs766910008; hg19: chr12-130647946; COSMIC: COSV57472804; COSMIC: COSV57472804;