12-6872461-GGG-ACT

Variant names:

• chr12-6872461-GGG-ACT
• NM_032641.4:c.439_441delCCCinsAGT
• SPSB2 p.Pro147Ser

Variant summary

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

The NM_032641.4(SPSB2):​c.439_441delCCCinsAGT​(p.Pro147Ser) 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPSB2 NM_032641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.42
• Publications: 0 publications found

Genes affected

SPSB2 (HGNC:29522): (splA/ryanodine receptor domain and SOCS box containing 2) This gene encodes a member of a subfamily of proteins containing a central SPRY (repeats in splA and RyR) domain and a C-terminal suppressor of cytokine signaling (SOCS) box. This protein plays a role in cell signaling. This gene is present in a gene-rich cluster on chromosome 12p13 in the vicinity of the CD4 antigen and triosephosphate isomerase genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032641.4. 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
	SPSB2	NM_032641.4	MANE Select	c.439_441delCCCinsAGT	p.Pro147Ser	missense	N/A	NP_116030.1	Q99619-1
	SPSB2	NM_001146316.2		c.439_441delCCCinsAGT	p.Pro147Ser	missense	N/A	NP_001139788.1	Q99619-1
	SPSB2	NM_001319670.2		c.439_441delCCCinsAGT	p.Pro147Ser	missense	N/A	NP_001306599.1	Q99619-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPSB2	ENST00000524270.6	TSL:1 MANE Select	c.439_441delCCCinsAGT	p.Pro147Ser	missense	N/A	ENSP00000428338.1	Q99619-1
	SPSB2	ENST00000523102.5	TSL:1	c.439_441delCCCinsAGT	p.Pro147Ser	missense	N/A	ENSP00000430872.1	Q99619-1
	SPSB2	ENST00000519357.1	TSL:2	c.439_441delCCCinsAGT	p.Pro147Ser	missense	N/A	ENSP00000431037.1	Q99619-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

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: chr12-6981625;