NM_002972.4:c.5664_5673delCTGCCTGTCG

Variant names:

• chr22-50447150-CCGACAGGCAG-C
• NM_002972.4:c.5664_5673delCTGCCTGTCG

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_002972.4(SBF1):​c.5664_5673delCTGCCTGTCG​(p.Ser1888ArgfsTer39) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SBF1 NM_002972.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.68

Genes affected

SBF1 (HGNC:10542): (SET binding factor 1) This gene encodes a member of the protein-tyrosine phosphatase family. However, the encoded protein does not appear to be a catalytically active phosphatase because it lacks several amino acids in the catalytic pocket. This protein contains a Guanine nucleotide exchange factor (GEF) domain which is necessary for its role in growth and differentiation. Mutations in this gene have been associated with Charcot-Marie-Tooth disease 4B3. Pseudogenes of this gene have been defined on chromosomes 1 and 8. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.00317 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBF1	NM_002972.4	c.5664_5673delCTGCCTGTCG	p.Ser1888ArgfsTer39	frameshift_variant	Exon 41 of 41	ENST00000380817.8	NP_002963.2
SBF1	NM_001410794.1	c.5667_5676delCTGCCTGTCG	p.Ser1889ArgfsTer39	frameshift_variant	Exon 41 of 41		NP_001397723.1
SBF1	NM_001365819.1	c.5589_5598delCTGCCTGTCG	p.Ser1863ArgfsTer39	frameshift_variant	Exon 40 of 40		NP_001352748.1
SBF1	NM_001410795.1	c.5586_5595delCTGCCTGTCG	p.Ser1862ArgfsTer39	frameshift_variant	Exon 40 of 40		NP_001397724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBF1	ENST00000380817.8	c.5664_5673delCTGCCTGTCG	p.Ser1888ArgfsTer39	frameshift_variant	Exon 41 of 41	1	NM_002972.4	ENSP00000370196.2

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Mar 11, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change results in a frameshift in the SBF1 gene (p.Ser1888Argfs*39). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 6 amino acid(s) of the SBF1 protein and extend the protein by 32 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SBF1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr22-50885579;