Genetic Variant SFRP1:p.Ala168Thr (chr8-41308658-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003012.5(SFRP1):c.502G>A(p.Ala168Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,030 control chromosomes in the GnomAD database, including 1 homozygotes. 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. A168S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 1 hom. )

Consequence

SFRP1
NM_003012.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.35

Publications

0 publications found

Variant links:

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]

SFRP1 links:

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ACMG classification

Classification was made for transcript

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=0.17688495).

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>A	p.Ala168Thr	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>A	p.Ala168Thr	missense	Exon 1 of 3	ENSP00000220772.3	Q8N474
	SFRP1	ENST00000923189.1		c.502G>A	p.Ala168Thr	missense	Exon 1 of 2	ENSP00000593248.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457030

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33400

American (AMR)

AF:

0.00

AC:

AN:

44400

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25990

East Asian (EAS)

AF:

0.00

AC:

AN:

39512

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109146

Other (OTH)

AF:

0.00

AC:

AN:

60060

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.32

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.81

M_CAP

Benign

0.037

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.2

PhyloP100

2.4

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.69

REVEL

Benign

0.15

Sift

Benign

0.27

Sift4G

Benign

0.32

Polyphen

0.067

Vest4

0.16

MutPred

0.39

Gain of glycosylation at A168 (P = 0.0019)

MVP

0.71

MPC

0.50

ClinPred

0.40

GERP RS

3.9

Varity_R

0.087

gMVP

0.60

Mutation Taster

=73/27

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over