22-50464722-G-T

Variant names:

• chr22-50464722-G-T
• NM_002972.4:c.1448C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002972.4(SBF1):​c.1448C>A​(p.Ala483Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,816 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SBF1 NM_002972.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

Genes affected

SBF1 (HGNC:10542): (SET binding factor 1) This gene encodes a member of the protein-tyrosine phosphatase family. However, the encoded protein does not appear to be a catalytically active phosphatase because it lacks several amino acids in the catalytic pocket. This protein contains a Guanine nucleotide exchange factor (GEF) domain which is necessary for its role in growth and differentiation. Mutations in this gene have been associated with Charcot-Marie-Tooth disease 4B3. Pseudogenes of this gene have been defined on chromosomes 1 and 8. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBF1	NM_002972.4	c.1448C>A	p.Ala483Asp	missense_variant	Exon 14 of 41	ENST00000380817.8	NP_002963.2
SBF1	NM_001410794.1	c.1451C>A	p.Ala484Asp	missense_variant	Exon 14 of 41		NP_001397723.1
SBF1	NM_001365819.1	c.1451C>A	p.Ala484Asp	missense_variant	Exon 14 of 40		NP_001352748.1
SBF1	NM_001410795.1	c.1448C>A	p.Ala483Asp	missense_variant	Exon 14 of 40		NP_001397724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBF1	ENST00000380817.8	c.1448C>A	p.Ala483Asp	missense_variant	Exon 14 of 41	1	NM_002972.4	ENSP00000370196.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454816 Hom.: 0 Cov.: 34 AF XY: 0.00000276 AC XY: 2 AN XY: 723430

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000608

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Benign	-0.0047
Eigen_PC	Benign	-0.077
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.71	T;T
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Uncertain	-0.094	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.29
Sift	Benign	0.21	T;T
Sift4G	Benign	0.23	T;T
Vest4		0.74
MutPred		0.30		.;Gain of ubiquitination at K489 (P = 0.0747);
MVP		0.47
ClinPred		0.67	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-50903151;