chr2-197400846-G-C

Variant names:

• chr2-197400846-G-C
• NM_012433.4:c.2587C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012433.4(SF3B1):​c.2587C>G​(p.Gln863Glu) 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 benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SF3B1 NM_012433.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.84

Genes affected

SF3B1 (HGNC:10768): (splicing factor 3b subunit 1) This gene encodes subunit 1 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and a 12S RNA unit, forms the U2 small nuclear ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a complex binds pre-mRNA upstream of the intron's branch site in a sequence independent manner and may anchor the U2 snRNP to the pre-mRNA. Splicing factor 3b is also a component of the minor U12-type spliceosome. The carboxy-terminal two-thirds of subunit 1 have 22 non-identical, tandem HEAT repeats that form rod-like, helical structures. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41570505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SF3B1	NM_012433.4	c.2587C>G	p.Gln863Glu	missense_variant	Exon 18 of 25	ENST00000335508.11	NP_036565.2
SF3B1	XM_047443838.1	c.2149C>G	p.Gln717Glu	missense_variant	Exon 15 of 22		XP_047299794.1
SF3B1	XM_047443839.1	c.2149C>G	p.Gln717Glu	missense_variant	Exon 15 of 22		XP_047299795.1
SF3B1	XM_047443840.1	c.2587C>G	p.Gln863Glu	missense_variant	Exon 18 of 22		XP_047299796.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3B1	ENST00000335508.11	c.2587C>G	p.Gln863Glu	missense_variant	Exon 18 of 25	1	NM_012433.4	ENSP00000335321.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.25
Sift	Benign	0.082	T
Sift4G	Benign	0.16	T
Polyphen		0.0050	B
Vest4		0.64
MutPred		0.32		Gain of disorder (P = 0.0599);
MVP		0.86
MPC		1.7
ClinPred		0.83	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.48
gMVP		0.79

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-198265570;