chr22-30342748-G-A

Variant names:

• chr22-30342748-G-A
• rs5753080
• NM_005877.6:c.726+57C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005877.6. 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
	SF3A1	NM_005877.6	MANE Select	c.726+57C>T		intron	N/A	NP_005868.1	Q15459-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3A1	ENST00000215793.13	TSL:1 MANE Select	c.726+57C>T		intron	N/A	ENSP00000215793.7	Q15459-1
	SF3A1	ENST00000872797.1		c.678+57C>T		intron	N/A	ENSP00000542856.1
	SF3A1	ENST00000872796.1		c.726+57C>T		intron	N/A	ENSP00000542855.1

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

African (AFR) AF: 0.972 AC: 22876 AN: 23524

American (AMR) AF: 0.851 AC: 35387 AN: 41570

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 20206 AN: 22704

East Asian (EAS) AF: 0.909 AC: 34098 AN: 37508

South Asian (SAS) AF: 0.920 AC: 70200 AN: 76320

European-Finnish (FIN) AF: 0.874 AC: 44171 AN: 50554

Middle Eastern (MID) AF: 0.941 AC: 4514 AN: 4796

European-Non Finnish (NFE) AF: 0.812 AC: 547529 AN: 674002

Other (OTH) AF: 0.857 AC: 37941 AN: 44280

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

African (AFR) AF: 0.967 AC: 40138 AN: 41508

American (AMR) AF: 0.872 AC: 13318 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 3094 AN: 3466

East Asian (EAS) AF: 0.905 AC: 4673 AN: 5166

South Asian (SAS) AF: 0.915 AC: 4403 AN: 4814

European-Finnish (FIN) AF: 0.888 AC: 9401 AN: 10586

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55315 AN: 67990

Other (OTH) AF: 0.880 AC: 1854 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.0
DANN	Benign	0.53
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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: rs5753080; hg19: chr22-30738737;