rs774759170

Variant names:

• chr1-37989579-T-C
• rs774759170
• NM_006802.4:c.113A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-37989579-T-C
• chr1-37989579-T-A
• chr1-37989579-T-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006802.4(SF3A3):​c.113A>G​(p.Asn38Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000096 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000092 (0 hom.)
• Consequence: SF3A3 NM_006802.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.49
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.133739).
• BS2: High AC in GnomAd4 at 21 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3A3	NM_006802.4	MANE Select	c.113A>G	p.Asn38Ser	missense	Exon 2 of 17	NP_006793.1	Q12874
	SF3A3	NM_001320830.2		c.113A>G	p.Asn38Ser	missense	Exon 2 of 15	NP_001307759.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3A3	ENST00000373019.5	TSL:1 MANE Select	c.113A>G	p.Asn38Ser	missense	Exon 2 of 17	ENSP00000362110.4	Q12874
	SF3A3	ENST00000896916.1		c.113A>G	p.Asn38Ser	missense	Exon 2 of 18	ENSP00000566975.1
	SF3A3	ENST00000963486.1		c.113A>G	p.Asn38Ser	missense	Exon 2 of 18	ENSP00000633545.1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152198 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000179 AC: 45 AN: 251096 AF XY: 0.000192

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000917 AC: 134 AN: 1461756 Hom.: 0 Cov.: 31 AF XY: 0.000102 AC XY: 74 AN XY: 727186

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.000112 AC: 5 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86250

European-Finnish (FIN) AF: 0.00152 AC: 81 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000306 AC: 34 AN: 1111956

Other (OTH) AF: 0.000132 AC: 8 AN: 60388

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152198 Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 12 AN XY: 74352

African (AFR) AF: 0.0000724 AC: 3 AN: 41462

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000325 Hom.: 0

Bravo AF: 0.0000604

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000181 AC: 22

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.044
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.22
Sift	Benign	0.054	T
Sift4G	Benign	0.40	T
Polyphen		0.041	B
Vest4		0.70
MVP		0.71
MPC		1.0
ClinPred		0.14	T
GERP RS		4.7
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.46
Mutation Taster		=71/29	polymorphism

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: rs774759170; hg19: chr1-38455251; COSMIC: COSV65955412; COSMIC: COSV65955412;