chr1-37984733-C-A

Variant names:

• chr1-37984733-C-A
• rs374095826
• NM_006802.4:c.350G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006802.4(SF3A3):​c.350G>T​(p.Arg117Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R117Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SF3A3 NM_006802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2173616).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006802.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3A3	NM_006802.4	MANE Select	c.350G>T	p.Arg117Leu	missense	Exon 5 of 17	NP_006793.1	Q12874
	SF3A3	NM_001320830.2		c.191G>T	p.Arg64Leu	missense	Exon 3 of 15	NP_001307759.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3A3	ENST00000373019.5	TSL:1 MANE Select	c.350G>T	p.Arg117Leu	missense	Exon 5 of 17	ENSP00000362110.4	Q12874
	SF3A3	ENST00000896916.1		c.350G>T	p.Arg117Leu	missense	Exon 5 of 18	ENSP00000566975.1
	SF3A3	ENST00000963486.1		c.404G>T	p.Arg135Leu	missense	Exon 6 of 18	ENSP00000633545.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.36
Sift	Benign	0.66	T
Sift4G	Benign	0.68	T
Polyphen		0.32	B
Vest4		0.39
MutPred		0.28		Loss of disorder (P = 0.0647)
MVP		0.47
MPC		1.5
ClinPred		0.96	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.68
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs374095826; hg19: chr1-38450405;