rs1288312315

Variant names:

• chr11-9784425-T-C
• rs1288312315
• NM_030962.4:c.5245A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030962.4(SBF2):​c.5245A>G​(p.Thr1749Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T1749T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SBF2 NM_030962.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.28
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35672048).

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.5245A>G	p.Thr1749Ala	missense	Exon 38 of 40	NP_112224.1
	SBF2	NM_001386339.1		c.5341A>G	p.Thr1781Ala	missense	Exon 39 of 41	NP_001373268.1
	SBF2	NM_001424318.1		c.5281A>G	p.Thr1761Ala	missense	Exon 39 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.5245A>G	p.Thr1749Ala	missense	Exon 38 of 40	ENSP00000256190.8
	SBF2	ENST00000689128.1		c.5341A>G	p.Thr1781Ala	missense	Exon 39 of 41	ENSP00000509587.1
	SBF2	ENST00000675281.2		c.5320A>G	p.Thr1774Ala	missense	Exon 39 of 41	ENSP00000502491.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251368 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461500 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727056

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111670

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	Benign	0.093
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Benign	0.92
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.060
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L
PhyloP100		3.3
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.14
Sift	Benign	0.50	T
Sift4G	Benign	0.28	T
Polyphen		0.37	B
Vest4		0.34
MutPred		0.60		Loss of phosphorylation at T1749 (P = 0.0309)
MVP		0.32
MPC		0.18
ClinPred		0.42	T
GERP RS		5.5
Varity_R		0.19
gMVP		0.38
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1288312315; hg19: chr11-9805972;