chr11-9781583-G-C

Variant names:

• chr11-9781583-G-C
• rs1554897834
• NM_030962.4:c.5375C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_030962.4(SBF2):​c.5375C>G​(p.Ala1792Gly) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1792V) has been classified 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: 8.02
• 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-AS1 (HGNC:27438): (SBF2 antisense RNA 1)

LOC105369149 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.764

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.5375C>G	p.Ala1792Gly	missense	Exon 39 of 40	NP_112224.1	Q86WG5-1
	SBF2	NM_001386339.1		c.5471C>G	p.Ala1824Gly	missense	Exon 40 of 41	NP_001373268.1	A0A8I5KQ02
	SBF2	NM_001424318.1		c.5411C>G	p.Ala1804Gly	missense	Exon 40 of 41	NP_001411247.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	ENST00000256190.13	TSL:1 MANE Select	c.5375C>G	p.Ala1792Gly	missense	Exon 39 of 40	ENSP00000256190.8	Q86WG5-1
	SBF2	ENST00000689128.1		c.5471C>G	p.Ala1824Gly	missense	Exon 40 of 41	ENSP00000509587.1	A0A8I5KQ02
	SBF2	ENST00000675281.2		c.5450C>G	p.Ala1817Gly	missense	Exon 40 of 41	ENSP00000502491.1	A0A6Q8PH13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

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	Benign	0.21
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.61
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.6	L
PhyloP100		8.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.47
Sift	Benign	0.030	D
Sift4G	Uncertain	0.048	D
Polyphen		0.61	P
Vest4		0.59
MutPred		0.49		Loss of stability (P = 0.0405)
MVP		0.80
MPC		0.20
ClinPred		0.77	D
GERP RS		5.8
Varity_R		0.50
gMVP		0.20
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1554897834; hg19: chr11-9803130;