Genetic Variant NM_007197.4:c.542C>G (chr12-130163484-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007197.4(FZD10):c.542C>G(p.Pro181Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,448,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

FZD10
NM_007197.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.362

Publications

0 publications found

Variant links:

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 links:

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

FZD10-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0652422).

BS2

High AC in GnomAdExome4 at 27 AD gene.

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.542C>G	p.Pro181Arg	missense	Exon 1 of 1	NP_009128.1	Q9ULW2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FZD10	ENST00000229030.5	TSL:6 MANE Select	c.542C>G	p.Pro181Arg	missense	Exon 1 of 1	ENSP00000229030.4	Q9ULW2
FZD10	ENST00000539839.1	TSL:6	c.444C>G	p.Pro148Pro	synonymous	Exon 1 of 1	ENSP00000438460.1	F5H450
FZD10-AS1	ENST00000815564.1		n.12G>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1448738

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

719624

show subpopulations

African (AFR)

AF:

0.000212

AC:

AN:

32958

American (AMR)

AF:

0.00

AC:

AN:

43000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25366

East Asian (EAS)

AF:

0.00

AC:

AN:

39502

South Asian (SAS)

AF:

0.00

AC:

AN:

85284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1105806

Other (OTH)

AF:

0.000318

AC:

AN:

59678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.32

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.48

M_CAP

Benign

0.073

MetaRNN

Benign

0.065

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.34

PhyloP100

0.36

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.56

REVEL

Benign

0.15

Sift

Benign

0.091

Sift4G

Benign

0.17

Polyphen

0.0010

Vest4

0.070

MutPred

0.25

Gain of solvent accessibility (P = 0.0789)

MVP

0.061

ClinPred

0.071

GERP RS

-8.3

Varity_R

0.046

gMVP

0.50

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over