chr11-9842711-C-A

Variant names:

• chr11-9842711-C-A
• rs138612196
• NM_030962.4:c.3170G>T

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.3170G>T​(p.Arg1057Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1057W) 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: 7.61
• 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics

ENSG00000255476 (HGNC:):

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, 0.849

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.3170G>T	p.Arg1057Leu	missense	Exon 25 of 40	NP_112224.1
	SBF2	NM_001386339.1		c.3170G>T	p.Arg1057Leu	missense	Exon 25 of 41	NP_001373268.1
	SBF2	NM_001424318.1		c.3206G>T	p.Arg1069Leu	missense	Exon 26 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.3170G>T	p.Arg1057Leu	missense	Exon 25 of 40	ENSP00000256190.8
	SBF2	ENST00000533770.6	TSL:1	c.3170G>T	p.Arg1057Leu	missense	Exon 25 of 26	ENSP00000509247.1
	ENSG00000255476	ENST00000533659.1	TSL:1	n.134+3435C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	1.4	L
PhyloP100		7.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.74	P
Vest4		0.87
MutPred		0.52		Loss of disorder (P = 0.0519)
MVP		0.95
MPC		0.23
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.63
gMVP		0.63
Mutation Taster		=62/38	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: rs138612196; hg19: chr11-9864258; COSMIC: COSV56311522; COSMIC: COSV56311522;