22-50446979-CGGGCGGGGCG-CGGGCGGGGCGGGGCGGGGCG

Variant names:

• chr22-50446979-C-CGGGCGGGGCG
• rs963346132
• NM_002972.4:c.*153_*162dupCGCCCCGCCC

Variant summary

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

The NM_002972.4(SBF1):​c.*153_*162dupCGCCCCGCCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00097 (2 hom.)
  • Failed GnomAD Quality Control
• 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.*153_*162dupCGCCCCGCCC		3_prime_UTR	Exon 41 of 41	NP_002963.2	O95248-5
	SBF1	NM_001410794.1		c.*153_*162dupCGCCCCGCCC		3_prime_UTR	Exon 41 of 41	NP_001397723.1	O95248-4
	SBF1	NM_001365819.1		c.*153_*162dupCGCCCCGCCC		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.*153_*162dupCGCCCCGCCC		3_prime_UTR	Exon 41 of 41	ENSP00000370196.2	O95248-5
	SBF1	ENST00000418590.4	TSL:1	c.*153_*162dupCGCCCCGCCC		3_prime_UTR	Exon 9 of 9	ENSP00000401538.2	H0Y5W8
	SBF1	ENST00000931646.1		c.*153_*162dupCGCCCCGCCC		3_prime_UTR	Exon 41 of 41	ENSP00000601705.1

Frequencies

GnomAD3 genomes AF: 0.000632 AC: 92 AN: 145548 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000849

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000476

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00951

Gnomad SAS AF: 0.00173

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000302

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000967 AC: 556 AN: 575060 Hom.: 2 Cov.: 7 AF XY: 0.000925 AC XY: 283 AN XY: 306026

African (AFR) AF: 0.00113 AC: 18 AN: 15944

American (AMR) AF: 0.000215 AC: 7 AN: 32542

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

East Asian (EAS) AF: 0.0142 AC: 451 AN: 31862

South Asian (SAS) AF: 0.000758 AC: 46 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: 0.0000346 AC: 12 AN: 346746

Other (OTH) AF: 0.000714 AC: 22 AN: 30818

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000659 AC: 96 AN: 145650 Hom.: 0 Cov.: 33 AF XY: 0.000731 AC XY: 52 AN XY: 71088

African (AFR) AF: 0.000947 AC: 38 AN: 40146

American (AMR) AF: 0.000476 AC: 7 AN: 14718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3404

East Asian (EAS) AF: 0.00953 AC: 42 AN: 4408

South Asian (SAS) AF: 0.00173 AC: 7 AN: 4042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000302 AC: 2 AN: 66288

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.0000544 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;