1-37989958-G-A

Position:

• chr1-37989958-G-A

Variant summary

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

The NM_006802.4(SF3A3):​c.8C>T​(p.Thr3Ile) variant causes a missense change. 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 NM_006802.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.98

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]

SF3A3 (HGNC:):

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=0.27328244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SF3A3	NM_006802.4	c.8C>T	p.Thr3Ile	missense_variant	1/17	ENST00000373019.5	NP_006793.1
SF3A3	NM_001320830.2	c.8C>T	p.Thr3Ile	missense_variant	1/15		NP_001307759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SF3A3	ENST00000373019.5	c.8C>T	p.Thr3Ile	missense_variant	1/17	1	NM_006802.4	ENSP00000362110.4
SF3A3	ENST00000461869.5	n.118C>T		non_coding_transcript_exon_variant	1/8	3
SF3A3	ENST00000462258.1	n.16C>T		non_coding_transcript_exon_variant	1/6	2
SF3A3	ENST00000470585.5	n.38C>T		non_coding_transcript_exon_variant	1/7	3

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 19, 2024

The c.8C>T (p.T3I) alteration is located in exon 1 (coding exon 1) of the SF3A3 gene. This alteration results from a C to T substitution at nucleotide position 8, causing the threonine (T) at amino acid position 3 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-4.3	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.54	P
Vest4		0.28
MutPred		0.31		Loss of phosphorylation at T3 (P = 0.0497);
MVP		0.71
MPC		2.1
ClinPred		1.0	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.75
gMVP		0.71

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: chr1-38455630;