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GeneBe

7-37909638-A-C

Variant summary

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

The NM_003014.4(SFRP4):c.834T>G(p.Asp278Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,428,842 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SFRP4
NM_003014.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.568
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15018427).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFRP4NM_003014.4 linkuse as main transcriptc.834T>G p.Asp278Glu missense_variant 5/6 ENST00000436072.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFRP4ENST00000436072.7 linkuse as main transcriptc.834T>G p.Asp278Glu missense_variant 5/61 NM_003014.4 P1
SFRP4ENST00000478975.1 linkuse as main transcriptn.202T>G non_coding_transcript_exon_variant 1/22
SFRP4ENST00000447200.2 linkuse as main transcript downstream_gene_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000140
AC:
2
AN:
1428842
Hom.:
0
Cov.:
26
AF XY:
0.00000141
AC XY:
1
AN XY:
710490
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000183
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 testingInvitaeApr 13, 2021Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with SFRP4-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glutamic acid at codon 278 of the SFRP4 protein (p.Asp278Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
12
DANN
Uncertain
0.98
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.0055
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.46
N
MutationTaster
Benign
1.0
D;N
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.0
N
REVEL
Benign
0.048
Sift
Benign
0.095
T
Sift4G
Benign
0.19
T
Polyphen
0.0020
B
Vest4
0.26
MutPred
0.45
Loss of sheet (P = 0.0457);
MVP
0.42
MPC
0.36
ClinPred
0.15
T
GERP RS
-7.3
Varity_R
0.057
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1554369743; hg19: chr7-37949240; API