rs1216288652

Variant names:

• chr7-73434341-C-G
• rs1216288652
• NM_003508.3:c.334C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-73434341-C-G
• chr7-73434341-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_003508.3(FZD9):​c.334C>G​(p.Arg112Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000436 in 1,582,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R112L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: FZD9 NM_003508.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.944
• Publications: 0 publications found

Genes affected

FZD9 (HGNC:4047): (frizzled class receptor 9) Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD9 gene is located within the Williams syndrome common deletion region of chromosome 7, and heterozygous deletion of the FZD9 gene may contribute to the Williams syndrome phenotype. FZD9 is expressed predominantly in brain, testis, eye, skeletal muscle, and kidney. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934
• BS2: High AC in GnomAdExome4 at 68 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003508.3. 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
	FZD9	NM_003508.3	MANE Select	c.334C>G	p.Arg112Gly	missense	Exon 1 of 1	NP_003499.1	O00144

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD9	ENST00000344575.5	TSL:6 MANE Select	c.334C>G	p.Arg112Gly	missense	Exon 1 of 1	ENSP00000345785.3	O00144

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152098 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000101 AC: 2 AN: 198312 AF XY: 0.0000181

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000221

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000475 AC: 68 AN: 1430402 Hom.: 0 Cov.: 33 AF XY: 0.0000380 AC XY: 27 AN XY: 711188

African (AFR) AF: 0.00 AC: 0 AN: 32152

American (AMR) AF: 0.00 AC: 0 AN: 42004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25654

East Asian (EAS) AF: 0.00 AC: 0 AN: 38382

South Asian (SAS) AF: 0.00 AC: 0 AN: 82578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.0000616 AC: 68 AN: 1103786

Other (OTH) AF: 0.00 AC: 0 AN: 59492

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152098 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74306

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.85	D
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.85	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	-0.054	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.94
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-4.8	D
REVEL	Pathogenic	0.67
Sift	Benign	0.15	T
Sift4G	Benign	0.066	T
Polyphen		0.049	B
Vest4		0.63
MutPred		0.82		Loss of loop (P = 0.1242)
MVP		0.62
ClinPred		0.53	D
GERP RS		2.7
Varity_R		0.33
gMVP		0.88
Mutation Taster		=23/77	disease causing

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: rs1216288652; hg19: chr7-72848671;