rs864622502

Variant names:

• chr11-9795936-C-T
• rs864622502
• NM_030962.4:c.4465G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_030962.4(SBF2):​c.4465G>A​(p.Glu1489Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SBF2 NM_030962.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.80
• Publications: 1 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-AS1 (HGNC:27438): (SBF2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	NM_030962.4	MANE Select	c.4465G>A	p.Glu1489Lys	missense	Exon 33 of 40	NP_112224.1
	SBF2	NM_001386339.1		c.4561G>A	p.Glu1521Lys	missense	Exon 34 of 41	NP_001373268.1
	SBF2	NM_001424318.1		c.4501G>A	p.Glu1501Lys	missense	Exon 34 of 41	NP_001411247.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	ENST00000256190.13	TSL:1 MANE Select	c.4465G>A	p.Glu1489Lys	missense	Exon 33 of 40	ENSP00000256190.8
	SBF2	ENST00000689128.1		c.4561G>A	p.Glu1521Lys	missense	Exon 34 of 41	ENSP00000509587.1
	SBF2	ENST00000675281.2		c.4540G>A	p.Glu1514Lys	missense	Exon 34 of 41	ENSP00000502491.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Charcot-Marie-Tooth disease type 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.68	D
MutationAssessor	Benign	1.5	L
PhyloP100		7.8
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.9	N
REVEL	Pathogenic	0.82
Sift	Benign	0.069	T
Sift4G	Benign	0.13	T
Polyphen		0.98	D
Vest4		0.89
MutPred		0.59		Gain of methylation at E1489 (P = 0.0098)
MVP		0.98
MPC		0.28
ClinPred		0.84	D
GERP RS		5.8
Varity_R		0.42
gMVP		0.58
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs864622502; hg19: chr11-9817483;