chr11-9789242-G-C

Variant names:

• chr11-9789242-G-C
• rs183468503
• NM_030962.4:c.4799C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001386339.1(SBF2):​c.4895C>G​(p.Thr1632Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. T1632I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SBF2 NM_001386339.1 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 4.14
• Publications: 4 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11137536).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386339.1. 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.4799C>G	p.Thr1600Ser	missense	Exon 35 of 40	NP_112224.1
	SBF2	NM_001386339.1		c.4895C>G	p.Thr1632Ser	missense	Exon 36 of 41	NP_001373268.1
	SBF2	NM_001424318.1		c.4835C>G	p.Thr1612Ser	missense	Exon 36 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.4799C>G	p.Thr1600Ser	missense	Exon 35 of 40	ENSP00000256190.8
	SBF2	ENST00000689128.1		c.4895C>G	p.Thr1632Ser	missense	Exon 36 of 41	ENSP00000509587.1
	SBF2	ENST00000675281.2		c.4874C>G	p.Thr1625Ser	missense	Exon 36 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, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Charcot-Marie-Tooth disease type 4 (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.95	L
PhyloP100		4.1
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.24
Sift	Benign	0.58	T
Sift4G	Benign	0.74	T
Polyphen		0.0080	B
Vest4		0.098
MutPred		0.34		Gain of disorder (P = 0.0271)
MVP		0.66
MPC		0.16
ClinPred		0.19	T
GERP RS		5.0
Varity_R		0.043
gMVP		0.25
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs183468503; hg19: chr11-9810789;