19-2248312-C-T

Variant names:

• chr19-2248312-C-T
• rs1384484910
• NM_007165.5:c.1161C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_007165.5(SF3A2):​c.1161C>T​(p.His387His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000016 in 1,250,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: SF3A2 NM_007165.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.281 with no splicing effect.

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.1161C>T	p.His387His	synonymous	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.1161C>T	p.His387His	synonymous	Exon 9 of 9	ENSP00000221494.3	Q15428
	SF3A2	ENST00000866932.1		c.1263C>T	p.His421His	synonymous	Exon 9 of 9	ENSP00000536991.1
	SF3A2	ENST00000866930.1		c.1161C>T	p.His387His	synonymous	Exon 10 of 10	ENSP00000536989.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.00 AC: 0 AN: 36492 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000160 AC: 2 AN: 1250886 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 605088

African (AFR) AF: 0.00 AC: 0 AN: 26030

American (AMR) AF: 0.00 AC: 0 AN: 16302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17928

East Asian (EAS) AF: 0.00 AC: 0 AN: 31358

South Asian (SAS) AF: 0.00 AC: 0 AN: 58754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4848

European-Non Finnish (NFE) AF: 0.00000197 AC: 2 AN: 1012740

Other (OTH) AF: 0.00 AC: 0 AN: 51898

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.63
PhyloP100		-0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1384484910; hg19: chr19-2248311;