rs778547916

Variant names:

• chr19-2247888-C-A
• rs778547916
• NM_007165.5:c.737C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-2247888-C-A
• chr19-2247888-C-T

Variant summary

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

The NM_007165.5(SF3A2):​c.737C>A​(p.Pro246Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,502 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict 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. P246L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SF3A2 NM_007165.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78
• Publications: 0 publications found

Genes affected

SF3A2 (HGNC:10766): (splicing factor 3a subunit 2) This gene encodes subunit 2 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 2 interacts with subunit 1 through its amino-terminus while the single zinc finger domain of subunit 2 plays a role in its binding to the 15S U2 snRNP. Subunit 2 may also function independently of its RNA splicing function as a microtubule-binding protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007165.5. 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
	SF3A2	NM_007165.5	MANE Select	c.737C>A	p.Pro246Gln	missense	Exon 9 of 9	NP_009096.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3A2	ENST00000221494.10	TSL:1 MANE Select	c.737C>A	p.Pro246Gln	missense	Exon 9 of 9	ENSP00000221494.3	Q15428
	SF3A2	ENST00000866932.1		c.839C>A	p.Pro280Gln	missense	Exon 9 of 9	ENSP00000536991.1
	SF3A2	ENST00000866930.1		c.737C>A	p.Pro246Gln	missense	Exon 10 of 10	ENSP00000536989.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426502 Hom.: 0 Cov.: 29 AF XY: 0.00000141 AC XY: 1 AN XY: 711430

African (AFR) AF: 0.00 AC: 0 AN: 33044

American (AMR) AF: 0.00 AC: 0 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25868

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 85800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 9.16e-7 AC: 1 AN: 1091894

Other (OTH) AF: 0.00 AC: 0 AN: 59404

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.68	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.067
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.082	B
Vest4		0.52
MutPred		0.28		Loss of glycosylation at P246 (P = 0.0068)
MVP		0.36
MPC		0.58
ClinPred		0.66	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.083
gMVP		0.23
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs778547916; hg19: chr19-2247887;