7-73434113-G-C

Variant names:

• chr7-73434113-G-C
• rs1554563156
• NM_003508.3:c.106G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_003508.3(FZD9):​c.106G>C​(p.Ala36Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,335,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. A36S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: FZD9 NM_003508.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082586795).
• BS2: High AC in GnomAdExome4 at 5 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.106G>C	p.Ala36Pro	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.106G>C	p.Ala36Pro	missense	Exon 1 of 1	ENSP00000345785.3	O00144

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000374 AC: 5 AN: 1335352 Hom.: 0 Cov.: 32 AF XY: 0.00000303 AC XY: 2 AN XY: 659442

African (AFR) AF: 0.00 AC: 0 AN: 27758

American (AMR) AF: 0.00 AC: 0 AN: 29878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21340

East Asian (EAS) AF: 0.00 AC: 0 AN: 31744

South Asian (SAS) AF: 0.00 AC: 0 AN: 69986

European-Finnish (FIN) AF: 0.0000281 AC: 1 AN: 35636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3972

European-Non Finnish (NFE) AF: 0.00000377 AC: 4 AN: 1059764

Other (OTH) AF: 0.00 AC: 0 AN: 55274

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	Benign	0.054
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.28	T
M_CAP	Pathogenic	0.49	D
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.16
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.17	N
REVEL	Benign	0.23
Sift	Benign	0.45	T
Sift4G	Benign	0.28	T
Polyphen		0.011	B
Vest4		0.074
MutPred		0.56		Gain of disorder (P = 0.0411)
MVP		0.16
ClinPred		0.035	T
GERP RS		-1.3
PromoterAI		0.13	Neutral
Varity_R		0.056
gMVP		0.55
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: rs1554563156; hg19: chr7-72848443;