2-24068422-C-T

Variant names:

• chr2-24068422-C-T
• NM_016047.4:c.187G>A

Variant summary

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

The NM_016047.4(SF3B6):​c.187G>A​(p.Val63Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SF3B6 NM_016047.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90

Genes affected

SF3B6 (HGNC:30096): (splicing factor 3b subunit 6) This gene encodes a 14 kDa protein subunit of the splicing factor 3b complex. Splicing factor 3b associates with both the U2 and U11/U12 small nuclear ribonucleoprotein complexes (U2 snRNP) of spliceosomes. This 14 kDa protein interacts directly with subunit 1 of the splicing factor 3b complex. This 14 kDa protein also interacts directly with the adenosine that carries out the first transesterification step of splicing at the pre-mRNA branch site. [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=0.39690346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SF3B6	NM_016047.4	c.187G>A	p.Val63Ile	missense_variant	Exon 3 of 4	ENST00000233468.5	NP_057131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3B6	ENST00000233468.5	c.187G>A	p.Val63Ile	missense_variant	Exon 3 of 4	1	NM_016047.4	ENSP00000233468.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.187G>A (p.V63I) alteration is located in exon 3 (coding exon 3) of the SF3B6 gene. This alteration results from a G to A substitution at nucleotide position 187, causing the valine (V) at amino acid position 63 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.18
Sift	Benign	0.15	T
Sift4G	Benign	0.070	T
Polyphen		0.11	B
Vest4		0.64
MutPred		0.61		Loss of phosphorylation at Y64 (P = 0.1198);
MVP		0.35
MPC		1.1
ClinPred		0.77	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.42

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-24291292;