8-41309154-GC-AT

Variant names:

• chr8-41309154-GC-AT
• NM_003012.5:c.5_6delGCinsAT
• SFRP1 p.Gly2Asp

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003012.5(SFRP1):​c.5_6delGCinsAT​(p.Gly2Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G2V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SFRP1 NM_003012.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003012.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP1	NM_003012.5	MANE Select	c.5_6delGCinsAT	p.Gly2Asp	missense	N/A	NP_003003.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP1	ENST00000220772.8	TSL:1 MANE Select	c.5_6delGCinsAT	p.Gly2Asp	missense	N/A	ENSP00000220772.3	Q8N474
	SFRP1	ENST00000923189.1		c.5_6delGCinsAT	p.Gly2Asp	missense	N/A	ENSP00000593248.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-41166673;