22-30352229-A-G

Variant names:

• chr22-30352229-A-G
• rs10427610
• NM_005877.6:c.185+722T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.957 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3A1	NM_005877.6	MANE Select	c.185+722T>C		intron	N/A	NP_005868.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3A1	ENST00000215793.13	TSL:1 MANE Select	c.185+722T>C		intron	N/A	ENSP00000215793.7
	SF3A1	ENST00000411423.1	TSL:4	n.63+4501T>C		intron	N/A	ENSP00000412715.1
	SF3A1	ENST00000447376.1	TSL:5	n.185+722T>C		intron	N/A	ENSP00000397267.1

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

African (AFR) AF: 0.965 AC: 39084 AN: 40506

American (AMR) AF: 0.870 AC: 13010 AN: 14956

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3003 AN: 3376

East Asian (EAS) AF: 0.904 AC: 4588 AN: 5078

South Asian (SAS) AF: 0.913 AC: 4293 AN: 4700

European-Finnish (FIN) AF: 0.884 AC: 9067 AN: 10252

Middle Eastern (MID) AF: 0.961 AC: 271 AN: 282

European-Non Finnish (NFE) AF: 0.813 AC: 54195 AN: 66658

Other (OTH) AF: 0.877 AC: 1818 AN: 2074

Alfa AF: 0.859 Hom.: 5647

Bravo AF: 0.876

Asia WGS AF: 0.917 AC: 3085 AN: 3364

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.23
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10427610; hg19: chr22-30748218;