NM_003013.3:c.220G>C

Variant names:

• chr4-153788616-C-G
• NM_003013.3:c.220G>C

Variant summary

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

The NM_003013.3(SFRP2):​c.220G>C​(p.Glu74Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SFRP2 NM_003013.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.34
• Publications: 0 publications found

Genes affected

SFRP2 (HGNC:10777): (secreted frizzled related protein 2) 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. SFRPs act as soluble modulators of Wnt signaling. Methylation of this gene is a potential marker for the presence of colorectal cancer. [provided by RefSeq, Jul 2008]

ENSG00000280241 (HGNC:58900):

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=0.08808452).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003013.3. 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
	SFRP2	NM_003013.3	MANE Select	c.220G>C	p.Glu74Gln	missense	Exon 1 of 3	NP_003004.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP2	ENST00000274063.5	TSL:1 MANE Select	c.220G>C	p.Glu74Gln	missense	Exon 1 of 3	ENSP00000274063.4
	SFRP2	ENST00000918154.1		c.220G>C	p.Glu74Gln	missense	Exon 1 of 3	ENSP00000588213.1
	ENSG00000280241	ENST00000839747.1		n.99+29050C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 74

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

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	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Benign	0.84
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.095
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.80	N
PhyloP100		4.3
PrimateAI	Benign	0.47	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.081
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.52		Gain of catalytic residue at E74 (P = 0.0966)
MVP		0.64
MPC		0.71
ClinPred		0.75	D
GERP RS		4.7
PromoterAI		-0.049	Neutral
Varity_R		0.33
gMVP		0.46
Mutation Taster		=82/18	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

hg19: chr4-154709768;