11-9845633-AG-TC

Variant names:

• chr11-9845633-AG-TC
• NM_030962.4:c.3041_3042delCTinsGA
• SBF2 p.Ala1014Gly

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_030962.4(SBF2):​c.3041_3042delCTinsGA​(p.Ala1014Gly) variant causes a missense change involving the alteration of a 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. A1014T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SBF2 NM_030962.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.59
• Publications: 0 publications found

Genes affected

SBF2 (HGNC:2135): (SET binding factor 2) This gene encodes a pseudophosphatase and member of the myotubularin-related protein family. This gene maps within the CMT4B2 candidate region of chromosome 11p15 and mutations in this gene have been associated with Charcot-Marie-Tooth Disease, type 4B2. [provided by RefSeq, Jul 2008]

SBF2 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 4B2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, Ambry Genetics, G2P, Orphanet

ENSG00000255476 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030962.4. 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
	SBF2	NM_030962.4	MANE Select	c.3041_3042delCTinsGA	p.Ala1014Gly	missense	N/A	NP_112224.1	Q86WG5-1
	SBF2	NM_001386339.1		c.3041_3042delCTinsGA	p.Ala1014Gly	missense	N/A	NP_001373268.1	A0A8I5KQ02
	SBF2	NM_001424318.1		c.3077_3078delCTinsGA	p.Ala1026Gly	missense	N/A	NP_001411247.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	ENST00000256190.13	TSL:1 MANE Select	c.3041_3042delCTinsGA	p.Ala1014Gly	missense	N/A	ENSP00000256190.8	Q86WG5-1
	SBF2	ENST00000533770.6	TSL:1	c.3041_3042delCTinsGA	p.Ala1014Gly	missense	N/A	ENSP00000509247.1	Q86WG5-3
	ENSG00000255476	ENST00000533659.1	TSL:1	n.134+6357_134+6358delAGinsTC		intron	N/A

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		9.6

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: chr11-9867180;