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GeneBe

7-37909673-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003014.4(SFRP4):c.799C>T(p.Leu267Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,417,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SFRP4
NM_003014.4 missense

Scores

7
4
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.30
Variant links:
Genes affected
SFRP4 (HGNC:10778): (secreted frizzled related protein 4) Secreted frizzled-related protein 4 (SFRP4) is 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. The expression of SFRP4 in ventricular myocardium correlates with apoptosis related gene expression. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.756

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFRP4NM_003014.4 linkuse as main transcriptc.799C>T p.Leu267Phe missense_variant 5/6 ENST00000436072.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFRP4ENST00000436072.7 linkuse as main transcriptc.799C>T p.Leu267Phe missense_variant 5/61 NM_003014.4 P1
SFRP4ENST00000447200.2 linkuse as main transcriptc.397C>T p.Leu133Phe missense_variant 6/65
SFRP4ENST00000478975.1 linkuse as main transcriptn.167C>T non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000129
AC:
3
AN:
232664
Hom.:
0
AF XY:
0.0000159
AC XY:
2
AN XY:
126146
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000336
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000185
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000212
AC:
3
AN:
1417778
Hom.:
0
Cov.:
24
AF XY:
0.00000284
AC XY:
2
AN XY:
705224
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000246
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000263
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.21e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeJul 19, 2022This variant has not been reported in the literature in individuals affected with SFRP4-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1416799). This variant is present in population databases (rs751834775, gnomAD 0.003%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 267 of the SFRP4 protein (p.Leu267Phe). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.57
BayesDel_addAF
Benign
-0.079
T
BayesDel_noAF
Benign
-0.25
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.31
T;T
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.81
T;T
M_CAP
Benign
0.056
D
MetaRNN
Pathogenic
0.76
D;D
MetaSVM
Benign
-0.77
T
MutationAssessor
Uncertain
2.0
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-2.0
N;D
REVEL
Uncertain
0.47
Sift
Uncertain
0.0010
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.67
MutPred
0.74
Gain of sheet (P = 0.0827);.;
MVP
0.87
MPC
1.2
ClinPred
0.91
D
GERP RS
6.0
Varity_R
0.53
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs751834775; hg19: chr7-37949275; API