rs2839998

Positions:

• chr22-30333518-G-A

Variant summary

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

The NM_005877.6(SF3A1):​c.*1076C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,242 control chromosomes in the GnomAD database, including 2,337 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 0.15 (2337 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: SF3A1 NM_005877.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SF3A1	NM_005877.6	c.*1076C>T		3_prime_UTR_variant	16/16	ENST00000215793.13	NP_005868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SF3A1	ENST00000215793	c.*1076C>T		3_prime_UTR_variant	16/16	1	NM_005877.6	ENSP00000215793.7

Frequencies

GnomAD3 genomes AF: 0.151 AC: 23041 AN: 152118 Hom.: 2335 Cov.: 33

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.151 AC: 23049 AN: 152238 Hom.: 2337 Cov.: 33 AF XY: 0.160 AC XY: 11887 AN XY: 74434

Gnomad4 AFR AF: 0.0363

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.154

Alfa AF: 0.176 Hom.: 3487

Bravo AF: 0.146

Asia WGS AF: 0.287 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.3
DANN	Benign	0.59

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: rs2839998; hg19: chr22-30729507;