chr7-73434060-C-T

Variant names:

• chr7-73434060-C-T
• rs1554563136
• NM_003508.3:c.53C>T

Variant summary

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

The NM_003508.3(FZD9):​c.53C>T​(p.Ala18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 151,664 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 8.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FZD9 NM_003508.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51
• 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: 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=0.13866127).

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.53C>T	p.Ala18Val	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.53C>T	p.Ala18Val	missense	Exon 1 of 1	ENSP00000345785.3	O00144

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151664 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.94e-7 AC: 1 AN: 1118118 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 532996

African (AFR) AF: 0.0000434 AC: 1 AN: 23026

American (AMR) AF: 0.00 AC: 0 AN: 8478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14902

East Asian (EAS) AF: 0.00 AC: 0 AN: 26708

South Asian (SAS) AF: 0.00 AC: 0 AN: 28664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3034

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 944012

Other (OTH) AF: 0.00 AC: 0 AN: 45268

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151664 Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2 AN XY: 74060

African (AFR) AF: 0.0000724 AC: 3 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10470

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67776

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.099
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.42	T
M_CAP	Pathogenic	0.82	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.5
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.41	N
REVEL	Benign	0.20
Sift	Benign	1.0	T
Sift4G	Benign	0.63	T
Polyphen		0.0020	B
Vest4		0.10
MutPred		0.37		Loss of MoRF binding (P = 0.2129)
MVP		0.16
ClinPred		0.14	T
GERP RS		3.4
PromoterAI		-0.072	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.070
gMVP		0.35
Mutation Taster		=85/15	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: rs1554563136; hg19: chr7-72848390;