1-37986909-A-G

Variant names:

• chr1-37986909-A-G
• rs12138115
• NM_006802.4:c.303+664T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006802.4(SF3A3):​c.303+664T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,502 control chromosomes in the GnomAD database, including 14,152 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 0.43 (14152 hom., cov: 29)
• Consequence: SF3A3 NM_006802.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922
• Publications: 15 publications found

Genes affected

SF3A3 (HGNC:10767): (splicing factor 3a subunit 3) This gene encodes subunit 3 of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer includes subunits 1, 2 and 3 and is necessary for the in vitro conversion of 15S U2 snRNP into an active 17S particle that performs pre-mRNA splicing. Subunit 3 interacts with subunit 1 through its amino-terminus while the zinc finger domain of subunit 3 plays a role in its binding to the 15S U2 snRNP. This gene has a pseudogene on chromosome 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006802.4. 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
	SF3A3	NM_006802.4	MANE Select	c.303+664T>C		intron	N/A	NP_006793.1
	SF3A3	NM_001320830.2		c.145-2130T>C		intron	N/A	NP_001307759.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3A3	ENST00000373019.5	TSL:1 MANE Select	c.303+664T>C		intron	N/A	ENSP00000362110.4
	SF3A3	ENST00000461869.5	TSL:3	n.255-2130T>C		intron	N/A
	SF3A3	ENST00000462258.1	TSL:2	n.311+664T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64964 AN: 151384 Hom.: 14136 Cov.: 29

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.429 AC: 65022 AN: 151502 Hom.: 14152 Cov.: 29 AF XY: 0.432 AC XY: 32014 AN XY: 74024

African (AFR) AF: 0.390 AC: 16105 AN: 41262

American (AMR) AF: 0.505 AC: 7672 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1477 AN: 3466

East Asian (EAS) AF: 0.658 AC: 3393 AN: 5160

South Asian (SAS) AF: 0.528 AC: 2538 AN: 4810

European-Finnish (FIN) AF: 0.402 AC: 4189 AN: 10432

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27994 AN: 67880

Other (OTH) AF: 0.448 AC: 945 AN: 2110

Alfa AF: 0.425 Hom.: 17391

Bravo AF: 0.442

Asia WGS AF: 0.558 AC: 1937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.27
PhyloP100		-0.92
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: rs12138115; hg19: chr1-38452581;