rs10427610

chr22-30352229-A-Gchr22-30352229-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.185+722T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 148,754 control chromosomes in the GnomAD database, including 57,031 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 0.87 (57031 hom., cov: 30)
• Consequence: SF3A1 NM_005877.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SF3A1	NM_005877.6	c.185+722T>C		intron_variant		ENST00000215793.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SF3A1	ENST00000215793.13	c.185+722T>C		intron_variant		1	NM_005877.6	P1
SF3A1	ENST00000411423.1	c.63+4501T>C		intron_variant, NMD_transcript_variant		4
SF3A1	ENST00000447376.1	c.185+722T>C		intron_variant, NMD_transcript_variant		5
SF3A1	ENST00000463818.1	n.284+722T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.874 AC: 129858 AN: 148652 Hom.: 56980 Cov.: 30

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.958

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.875

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.874 AC: 129958 AN: 148754 Hom.: 57031 Cov.: 30 AF XY: 0.878 AC XY: 63829 AN XY: 72658

Gnomad4 AFR AF: 0.965

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.913

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.877

Alfa AF: 0.853 Hom.: 5280

Bravo AF: 0.876

Asia WGS AF: 0.917 AC: 3085 AN: 3364

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.28
Dann	Benign	0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10427610; hg19: chr22-30748218;