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GeneBe

7-37907582-G-A

Variant summary

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

The NM_003014.4(SFRP4):c.938C>T(p.Pro313Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 6.8e-7 ( 0 hom. )

Consequence

SFRP4
NM_003014.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.09
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=0.113688976).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFRP4NM_003014.4 linkuse as main transcriptc.938C>T p.Pro313Leu missense_variant 6/6 ENST00000436072.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFRP4ENST00000436072.7 linkuse as main transcriptc.938C>T p.Pro313Leu missense_variant 6/61 NM_003014.4 P1
SFRP4ENST00000478975.1 linkuse as main transcriptn.306C>T non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461468
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727052
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
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

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 16, 2022The c.938C>T (p.P313L) alteration is located in exon 6 (coding exon 6) of the SFRP4 gene. This alteration results from a C to T substitution at nucleotide position 938, causing the proline (P) at amino acid position 313 to be replaced by a leucine (L). 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
Benign
0.069
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.41
N
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.0075
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.55
N
MutationTaster
Benign
0.85
N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
0.15
N
REVEL
Benign
0.057
Sift
Uncertain
0.0060
D
Sift4G
Benign
0.12
T
Polyphen
0.020
B
Vest4
0.15
MutPred
0.20
Loss of glycosylation at P313 (P = 0.0087);
MVP
0.76
MPC
0.39
ClinPred
0.52
D
GERP RS
5.8
Varity_R
0.061
gMVP
0.17

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: rs1314804498; hg19: chr7-37947184; COSMIC: COSV71412370; COSMIC: COSV71412370; API