1-37979526-G-C

Position:

• chr1-37979526-G-C

Variant summary

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

The ENST00000373019.5(SF3A3):​c.698C>G​(p.Thr233Arg) 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: 32)
• Consequence: SF3A3 ENST00000373019.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.58

Genes affected

SF3A3 (HGNC:10767): (splicing factor 3a subunit 3) This gene encodes subunit 3 of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer includes subunits 1, 2 and 3 and is necessary for the in vitro conversion of 15S U2 snRNP into an active 17S particle that performs pre-mRNA splicing. Subunit 3 interacts with subunit 1 through its amino-terminus while the zinc finger domain of subunit 3 plays a role in its binding to the 15S U2 snRNP. This gene has a pseudogene on chromosome 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

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/exons	MANE	Protein	UniProt
SF3A3	NM_006802.4	c.698C>G	p.Thr233Arg	missense_variant	9/17	ENST00000373019.5	NP_006793.1
SF3A3	NM_001320830.2	c.539C>G	p.Thr180Arg	missense_variant	7/15		NP_001307759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SF3A3	ENST00000373019.5	c.698C>G	p.Thr233Arg	missense_variant	9/17	1	NM_006802.4	ENSP00000362110	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2024

The c.698C>G (p.T233R) alteration is located in exon 9 (coding exon 9) of the SF3A3 gene. This alteration results from a C to G substitution at nucleotide position 698, causing the threonine (T) at amino acid position 233 to be replaced by an arginine (R). 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	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.053	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.42
Sift	Benign	0.16	T
Sift4G	Benign	0.56	T
Polyphen		0.026	B
Vest4		0.48
MutPred		0.24		Gain of catalytic residue at T233 (P = 0.0379);
MVP		0.46
MPC		1.7
ClinPred		0.90	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.55
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.28		Position offset: 3

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: chr1-38445198;