rs10376

chr22-30332367-A-Cchr22-30332367-A-T

Variant summary

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

The NM_005877.6(SF3A1):c.*2227T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,248 control chromosomes in the GnomAD database, including 58,674 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 (58668 hom., cov: 31)
  • Exomes 𝑓: 1.0 (6 hom.)
• Consequence: SF3A1 NM_005877.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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=-0.91).
• 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.*2227T>G		3_prime_UTR_variant	16/16	ENST00000215793.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SF3A1	ENST00000215793.13	c.*2227T>G		3_prime_UTR_variant	16/16	1	NM_005877.6	P1

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133121 AN: 152118 Hom.: 58609 Cov.: 31

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.878

GnomAD4 exome AF: 1.00 AC: 12 AN: 12 Hom.: 6 Cov.: 0 AF XY: 1.00 AC XY: 8 AN XY: 8

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.875 AC: 133237 AN: 152236 Hom.: 58668 Cov.: 31 AF XY: 0.880 AC XY: 65507 AN XY: 74436

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.879

Alfa AF: 0.839 Hom.: 16777

Bravo AF: 0.875

Asia WGS AF: 0.923 AC: 3211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.86
Dann	Benign	0.43

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: rs10376; hg19: chr22-30728356;