rs5753080

chr22-30342748-G-Achr22-30342748-G-Cchr22-30342748-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005877.6(SF3A1):c.726+57C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 1,127,378 control chromosomes in the GnomAD database, including 401,982 homozygotes. 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: 𝑓 0.88 (58620 hom., cov: 29)
  • Exomes 𝑓: 0.84 (343362 hom.)
• Consequence: SF3A1 NM_005877.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523

Genes affected

SF3A1 (HGNC:10765): (splicing factor 3a subunit 1) This gene encodes a subunit of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer is a component of the mature U2 small nuclear ribonucleoprotein particle (snRNP). U2 small nuclear ribonucleoproteins play a critical role in spliceosome assembly and pre-mRNA splicing. [provided by RefSeq, Aug 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SF3A1	NM_005877.6	c.726+57C>T		intron_variant		ENST00000215793.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SF3A1	ENST00000215793.13	c.726+57C>T		intron_variant		1	NM_005877.6	P1
SF3A1	ENST00000471037.1	n.354C>T		non_coding_transcript_exon_variant	2/2	3
SF3A1	ENST00000411423.1	c.64-3569C>T		intron_variant, NMD_transcript_variant		4
SF3A1	ENST00000447376.1	c.*68+57C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133022 AN: 152002 Hom.: 58561 Cov.: 29

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.879

GnomAD4 exome AF: 0.838 AC: 816922 AN: 975258 Hom.: 343362 Cov.: 13 AF XY: 0.840 AC XY: 425946 AN XY: 506844

Gnomad4 AFR exome AF: 0.972

Gnomad4 AMR exome AF: 0.851

Gnomad4 ASJ exome AF: 0.890

Gnomad4 EAS exome AF: 0.909

Gnomad4 SAS exome AF: 0.920

Gnomad4 FIN exome AF: 0.874

Gnomad4 NFE exome AF: 0.812

Gnomad4 OTH exome AF: 0.857

GnomAD4 genome AF: 0.875 AC: 133138 AN: 152120 Hom.: 58620 Cov.: 29 AF XY: 0.880 AC XY: 65445 AN XY: 74364

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.893

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.880

Alfa AF: 0.850 Hom.: 8079

Bravo AF: 0.875

Asia WGS AF: 0.922 AC: 3207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	7.0
Dann	Benign	0.53

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

LitVar

Other links and lift over

dbSNP: rs5753080; hg19: chr22-30738737;