rs200092271

Variant names:

• chr12-130163289-A-G
• rs200092271
• NM_007197.4:c.347A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_007197.4(FZD10):​c.347A>G​(p.Lys116Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000282 in 1,612,916 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (1 hom.)
• Consequence: FZD10 NM_007197.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91
• Publications: 2 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.122487515).
• BS2: High AC in GnomAd4 at 28 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.347A>G	p.Lys116Arg	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.347A>G	p.Lys116Arg	missense	Exon 1 of 1	ENSP00000229030.4	Q9ULW2
	FZD10	ENST00000539839.1	TSL:6	c.249A>G	p.Gln83Gln	synonymous	Exon 1 of 1	ENSP00000438460.1	F5H450
	FZD10-AS1	ENST00000815564.1		n.118+89T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152072 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000204 AC: 51 AN: 250362 AF XY: 0.000236

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000354

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000292 AC: 427 AN: 1460844 Hom.: 1 Cov.: 35 AF XY: 0.000268 AC XY: 195 AN XY: 726758

African (AFR) AF: 0.0000597 AC: 2 AN: 33474

American (AMR) AF: 0.000179 AC: 8 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000357 AC: 397 AN: 1111944

Other (OTH) AF: 0.000331 AC: 20 AN: 60378

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152072 Hom.: 0 Cov.: 33 AF XY: 0.000229 AC XY: 17 AN XY: 74292

African (AFR) AF: 0.0000241 AC: 1 AN: 41414

American (AMR) AF: 0.000720 AC: 11 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68012

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000199 Hom.: 0

Bravo AF: 0.000249

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000198 AC: 24

EpiCase AF: 0.000709

EpiControl AF: 0.000711

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	0.080
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.29	N
PhyloP100		4.9
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.28
Sift	Benign	0.32	T
Sift4G	Benign	0.28	T
Polyphen		0.0020	B
Vest4		0.19
MVP		0.32
ClinPred		0.018	T
GERP RS		3.7
Varity_R		0.085
gMVP		0.34
Mutation Taster		=88/12	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: rs200092271; hg19: chr12-130647834;