1-37979048-G-A

Variant names:

• chr1-37979048-G-A
• NM_006802.4:c.767C>T

Variant summary

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

The NM_006802.4(SF3A3):​c.767C>T​(p.Ala256Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 9.95

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 rank	MANE	Protein	UniProt
SF3A3	NM_006802.4	c.767C>T	p.Ala256Val	missense_variant	Exon 10 of 17	ENST00000373019.5	NP_006793.1
SF3A3	NM_001320830.2	c.608C>T	p.Ala203Val	missense_variant	Exon 8 of 15		NP_001307759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3A3	ENST00000373019.5	c.767C>T	p.Ala256Val	missense_variant	Exon 10 of 17	1	NM_006802.4	ENSP00000362110.4
SF3A3	ENST00000460925.1	n.152C>T		non_coding_transcript_exon_variant	Exon 1 of 4	2
SF3A3	ENST00000461869.5	n.718C>T		non_coding_transcript_exon_variant	Exon 8 of 8	3
SF3A3	ENST00000489537.5	n.726C>T		non_coding_transcript_exon_variant	Exon 9 of 10	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.767C>T (p.A256V) alteration is located in exon 10 (coding exon 10) of the SF3A3 gene. This alteration results from a C to T substitution at nucleotide position 767, causing the alanine (A) at amino acid position 256 to be replaced by a valine (V). 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	0.95
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	23
DANN	Benign	0.94
DEOGEN2	Benign	0.050	T
Eigen	Benign	0.079
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.8	L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.21
Sift	Benign	0.19	T
Sift4G	Benign	0.30	T
Polyphen		0.16	B
Vest4		0.66
MutPred		0.44		Loss of disorder (P = 0.0389);
MVP		0.45
MPC		1.3
ClinPred		0.78	D
GERP RS		5.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.31
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr1-38444720; COSMIC: COSV65955608; COSMIC: COSV65955608;