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GeneBe

8-41265178-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_003012.5(SFRP1):c.934G>A(p.Val312Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,314,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000044 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SFRP1
NM_003012.5 missense

Scores

10
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.274341).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFRP1NM_003012.5 linkuse as main transcriptc.934G>A p.Val312Met missense_variant 3/3 ENST00000220772.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFRP1ENST00000220772.8 linkuse as main transcriptc.934G>A p.Val312Met missense_variant 3/31 NM_003012.5 P1
SFRP1ENST00000379845.3 linkuse as main transcriptc.526G>A p.Val176Met missense_variant 3/32

Frequencies

GnomAD3 genomes
AF:
0.0000440
AC:
6
AN:
136216
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000106
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000125
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000157
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000254
AC:
6
AN:
236400
Hom.:
0
AF XY:
0.0000235
AC XY:
3
AN XY:
127560
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000571
Gnomad SAS exome
AF:
0.0000688
Gnomad FIN exome
AF:
0.0000960
Gnomad NFE exome
AF:
0.00000952
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000178
AC:
21
AN:
1178692
Hom.:
0
Cov.:
32
AF XY:
0.0000206
AC XY:
12
AN XY:
582388
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000127
Gnomad4 SAS exome
AF:
0.0000375
Gnomad4 FIN exome
AF:
0.0000319
Gnomad4 NFE exome
AF:
0.0000151
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000440
AC:
6
AN:
136216
Hom.:
0
Cov.:
31
AF XY:
0.0000153
AC XY:
1
AN XY:
65438
show subpopulations
Gnomad4 AFR
AF:
0.000106
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000125
Gnomad4 NFE
AF:
0.0000157
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000602
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 25, 2022The c.934G>A (p.V312M) alteration is located in exon 3 (coding exon 3) of the SFRP1 gene. This alteration results from a G to A substitution at nucleotide position 934, causing the valine (V) at amino acid position 312 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.34
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.53
D;T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.047
D
MetaRNN
Benign
0.27
T;T
MetaSVM
Benign
-0.51
T
MutationAssessor
Benign
1.6
L;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.68
N;N
REVEL
Benign
0.16
Sift
Uncertain
0.021
D;D
Sift4G
Uncertain
0.031
D;D
Polyphen
0.99
D;.
Vest4
0.41
MutPred
0.18
Gain of disorder (P = 0.0547);.;
MVP
0.80
MPC
0.66
ClinPred
0.25
T
GERP RS
4.9
Varity_R
0.073
gMVP
0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs765603358; hg19: chr8-41122697; COSMIC: COSV55172707; API