7-56064339-CCC-GCG

Variant names:

• chr7-56064339-CCC-GCG
• NM_015411.4:c.28_30delCCCinsGCG
• SUMF2 p.Pro10Ala

Variant summary

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

The NM_015411.4(SUMF2):​c.28_30delCCCinsGCG​(p.Pro10Ala) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P10R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUMF2 NM_015411.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 0 publications found

Genes affected

SUMF2 (HGNC:20415): (sulfatase modifying factor 2) The catalytic sites of sulfatases are only active if they contain a unique amino acid, C-alpha-formylglycine (FGly). The FGly residue is posttranslationally generated from a cysteine by enzymes with FGly-generating activity. The gene described in this record is a member of the sulfatase-modifying factor family and encodes a protein with a DUF323 domain that localizes to the lumen of the endoplasmic reticulum. This protein has low levels of FGly-generating activity but can heterodimerize with another family member - a protein with high levels of FGly-generating activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015411.4. 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
	SUMF2	NM_015411.4	MANE Select	c.28_30delCCCinsGCG	p.Pro10Ala	missense	N/A	NP_056226.3	Q8NBJ7-1
	SUMF2	NM_001366648.2		c.28_30delCCCinsGCG	p.Pro10Ala	missense	N/A	NP_001353577.1	C9J660
	SUMF2	NM_001130069.4		c.28_30delCCCinsGCG	p.Pro10Ala	missense	N/A	NP_001123541.2	Q8NBJ7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF2	ENST00000434526.8	TSL:1 MANE Select	c.28_30delCCCinsGCG	p.Pro10Ala	missense	N/A	ENSP00000400922.3	Q8NBJ7-1
	SUMF2	ENST00000342190.11	TSL:1	c.28_30delCCCinsGCG	p.Pro10Ala	missense	N/A	ENSP00000341938.7	Q8NBJ7-3
	SUMF2	ENST00000395436.7	TSL:1	c.28_30delCCCinsGCG	p.Pro10Ala	missense	N/A	ENSP00000378824.3	A8MXB9

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		-1.1

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: chr7-56132032;