NM_003012.5:c.502G>C

Variant names:

• chr8-41308658-C-G
• rs763220830
• NM_003012.5:c.502G>C

Variant summary

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

The NM_003012.5(SFRP1):​c.502G>C​(p.Ala168Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. A168S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SFRP1 NM_003012.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35
• Publications: 0 publications found

Genes affected

SFRP1 (HGNC:10776): (secreted frizzled related protein 1) This gene encodes a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. Members of this family act as soluble modulators of Wnt signaling; epigenetic silencing of SFRP genes leads to deregulated activation of the Wnt-pathway which is associated with cancer. This gene may also be involved in determining the polarity of photoreceptor cells in the retina. [provided by RefSeq, Sep 2009]

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=0.18702355).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003012.5. 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
	SFRP1	NM_003012.5	MANE Select	c.502G>C	p.Ala168Pro	missense	Exon 1 of 3	NP_003003.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP1	ENST00000220772.8	TSL:1 MANE Select	c.502G>C	p.Ala168Pro	missense	Exon 1 of 3	ENSP00000220772.3	Q8N474
	SFRP1	ENST00000923189.1		c.502G>C	p.Ala168Pro	missense	Exon 1 of 2	ENSP00000593248.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.86	L
PhyloP100		2.4
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.010	N
REVEL	Uncertain	0.35
Sift	Benign	0.42	T
Sift4G	Benign	0.29	T
Polyphen		0.0030	B
Vest4		0.28
MutPred		0.57		Gain of disorder (P = 0.0242)
MVP		0.71
MPC		1.3
ClinPred		0.66	D
GERP RS		3.9
Varity_R		0.21
gMVP		0.88
Mutation Taster		=70/30	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: rs763220830; hg19: chr8-41166177;