22-50446979-CGGGCGGGGCG-CGGGCGGGGCGGGGCGGGGCGGGGCG

Variant names:

• chr22-50446979-C-CGGGCGGGGCGGGGCG
• rs963346132
• NM_002972.4:c.*148_*162dupCGCCCCGCCCCGCCC

Variant summary

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

The NM_002972.4(SBF1):​c.*148_*162dupCGCCCCGCCCCGCCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000174 in 575,060 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: SBF1 NM_002972.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319
• Publications: 0 publications found

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]

SBF1 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 4B3

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, PanelApp Australia, Ambry Genetics

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002972.4. 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
	SBF1	NM_002972.4	MANE Select	c.*148_*162dupCGCCCCGCCCCGCCC		3_prime_UTR	Exon 41 of 41	NP_002963.2	O95248-5
	SBF1	NM_001410794.1		c.*148_*162dupCGCCCCGCCCCGCCC		3_prime_UTR	Exon 41 of 41	NP_001397723.1	O95248-4
	SBF1	NM_001365819.1		c.*148_*162dupCGCCCCGCCCCGCCC		3_prime_UTR	Exon 40 of 40	NP_001352748.1	O95248-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF1	ENST00000380817.8	TSL:1 MANE Select	c.*148_*162dupCGCCCCGCCCCGCCC		3_prime_UTR	Exon 41 of 41	ENSP00000370196.2	O95248-5
	SBF1	ENST00000418590.4	TSL:1	c.*148_*162dupCGCCCCGCCCCGCCC		3_prime_UTR	Exon 9 of 9	ENSP00000401538.2	H0Y5W8
	SBF1	ENST00000931646.1		c.*148_*162dupCGCCCCGCCCCGCCC		3_prime_UTR	Exon 41 of 41	ENSP00000601705.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000174 AC: 1 AN: 575060 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 306026

African (AFR) AF: 0.00 AC: 0 AN: 15944

American (AMR) AF: 0.00 AC: 0 AN: 32542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19064

East Asian (EAS) AF: 0.0000314 AC: 1 AN: 31862

South Asian (SAS) AF: 0.00 AC: 0 AN: 60654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2432

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 346746

Other (OTH) AF: 0.00 AC: 0 AN: 30818

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.32

Splicing

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

Other links and lift over

dbSNP: rs963346132; hg19: chr22-50885408;