8-41308658-C-T

Variant names:

• chr8-41308658-C-T
• NM_003012.5:c.502G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003012.5(SFRP1):​c.502G>A​(p.Ala168Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (1 hom.)
• Consequence: SFRP1 NM_003012.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35

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]

ACMG classification

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=0.17688495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFRP1	NM_003012.5	c.502G>A	p.Ala168Thr	missense_variant	Exon 1 of 3	ENST00000220772.8	NP_003003.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFRP1	ENST00000220772.8	c.502G>A	p.Ala168Thr	missense_variant	Exon 1 of 3	1	NM_003012.5	ENSP00000220772.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457030 Hom.: 1 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724202

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: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.15
Sift	Benign	0.27	T
Sift4G	Benign	0.32	T
Polyphen		0.067	B
Vest4		0.16
MutPred		0.39		Gain of glycosylation at A168 (P = 0.0019);
MVP		0.71
MPC		0.50
ClinPred		0.40	T
GERP RS		3.9
Varity_R		0.087
gMVP		0.60

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: chr8-41166177;