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GeneBe

8-41303480-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003012.5(SFRP1):c.603T>A(p.His201Gln) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

SFRP1
NM_003012.5 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21795237).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFRP1NM_003012.5 linkuse as main transcriptc.603T>A p.His201Gln missense_variant 2/3 ENST00000220772.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFRP1ENST00000220772.8 linkuse as main transcriptc.603T>A p.His201Gln missense_variant 2/31 NM_003012.5 P1
SFRP1ENST00000379845.3 linkuse as main transcriptc.195T>A p.His65Gln missense_variant 2/32

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
31

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 GeneticsJan 31, 2024The c.603T>A (p.H201Q) alteration is located in exon 2 (coding exon 2) of the SFRP1 gene. This alteration results from a T to A substitution at nucleotide position 603, causing the histidine (H) at amino acid position 201 to be replaced by a glutamine (Q). 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
Pathogenic
0.82
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
18
DANN
Benign
0.92
DEOGEN2
Benign
0.29
T;T
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.31
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.76
T;T
M_CAP
Benign
0.0098
T
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.92
L;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.070
Sift
Benign
0.67
T;T
Sift4G
Benign
0.68
T;T
Polyphen
0.043
B;.
Vest4
0.49
MutPred
0.45
Gain of helix (P = 0.0496);.;
MVP
0.41
MPC
0.65
ClinPred
0.20
T
GERP RS
3.2
Varity_R
0.17
gMVP
0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-41160999; API