Genetic Variant NM_030962.4:c.4693A>C (chr11-9790561-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030962.4(SBF2):c.4693A>C(p.Ile1565Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,431,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign 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. I1565V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SBF2
NM_030962.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20

Publications

0 publications found

Variant links:

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 links:

SBF2-AS1 (HGNC:27438): (SBF2 antisense RNA 1)

SBF2-AS1 links:

LOC105369149 (HGNC:):

LOC105369149 links:

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ACMG classification

Classification was made for transcript

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=0.11513966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBF2	NM_030962.4 link	c.4693A>C	p.Ile1565Leu	missense_variant	Exon 34 of 40	ENST00000256190.13	NP_112224.1	Q86WG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBF2	ENST00000256190.13 link	c.4693A>C	p.Ile1565Leu	missense_variant	Exon 34 of 40	1	NM_030962.4	ENSP00000256190.8		Q86WG5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000408

AC:

AN:

244936

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000629

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1431668

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713052

show subpopulations

African (AFR)

AF:

0.0000306

AC:

AN:

32690

American (AMR)

AF:

0.00

AC:

AN:

43426

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25824

East Asian (EAS)

AF:

0.00

AC:

AN:

39472

South Asian (SAS)

AF:

0.00

AC:

AN:

83156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

9.18e-7

AC:

AN:

1088748

Other (OTH)

AF:

0.00

AC:

AN:

59402

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.650

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.075

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.52

M_CAP

Benign

0.013

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.66

MutationAssessor

Benign

-0.19

PhyloP100

1.2

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.29

REVEL

Benign

0.12

Sift

Benign

0.35

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.20

MutPred

0.35

Loss of methylation at K1569 (P = 0.0884);

MVP

0.68

MPC

0.18

ClinPred

0.067

GERP RS

3.7

Varity_R

0.063

gMVP

0.25

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over