chr4-153788745-G-T

Variant names:

• chr4-153788745-G-T
• rs144480119
• NM_003013.3:c.91C>A

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.91C>A​(p.Pro31Thr) 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. 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. P31A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SFRP2 NM_003013.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.06
• 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=0.22212243).

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.91C>A	p.Pro31Thr	missense	Exon 1 of 3	NP_003004.1	A0A140VJU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP2	ENST00000274063.5	TSL:1 MANE Select	c.91C>A	p.Pro31Thr	missense	Exon 1 of 3	ENSP00000274063.4	Q96HF1
	SFRP2	ENST00000918154.1		c.91C>A	p.Pro31Thr	missense	Exon 1 of 3	ENSP00000588213.1
	ENSG00000280241	ENST00000839747.1		n.99+29179G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

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	0.086
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.75
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.096
Sift	Benign	0.24	T
Sift4G	Benign	0.46	T
Polyphen		0.036	B
Vest4		0.38
MutPred		0.47		Gain of ubiquitination at K36 (P = 0.0898)
MVP		0.68
MPC		0.85
ClinPred		0.36	T
GERP RS		2.7
PromoterAI		0.022	Neutral
Varity_R		0.17
gMVP		0.63
Mutation Taster		=69/31	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: rs144480119; hg19: chr4-154709897;