rs540520

Variant names:

• chr12-120473983-G-A
• rs540520
• ENST00000706469.1:c.89+653C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-120473983-G-A
• chr12-120473983-G-C

Variant summary

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

The ENST00000706469.1(SRSF9):​c.89+653C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 150,256 control chromosomes in the GnomAD database, including 14,131 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 0.40 (14131 hom., cov: 29)
• Consequence: SRSF9 ENST00000706469.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 20 publications found

Genes affected

SRSF9 (HGNC:10791): (serine and arginine rich splicing factor 9) The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Two pseudogenes, one on chromosome 15 and the other on chromosome 21, have been found for this gene. [provided by RefSeq, Sep 2010]

DYNLL1 (HGNC:15476): (dynein light chain LC8-type 1) Cytoplasmic dyneins are large enzyme complexes with a molecular mass of about 1,200 kD. They contain two force-producing heads formed primarily from dynein heavy chains, and stalks linking the heads to a basal domain, which contains a varying number of accessory intermediate chains. The complex is involved in intracellular transport and motility. The protein described in this record is a light chain and exists as part of this complex but also physically interacts with and inhibits the activity of neuronal nitric oxide synthase. Binding of this protein destabilizes the neuronal nitric oxide synthase dimer, a conformation necessary for activity, and it may regulate numerous biologic processes through its effects on nitric oxide synthase activity. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000706469.1. 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
	DYNLL1	NM_001037494.2		c.-7+3879G>A		intron	N/A	NP_001032583.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF9	ENST00000706469.1		c.89+653C>T		intron	N/A	ENSP00000516402.1
	DYNLL1	ENST00000392509.6	TSL:3	c.-7+3879G>A		intron	N/A	ENSP00000376297.2
	DYNLL1	ENST00000548342.5	TSL:2	c.-144+3879G>A		intron	N/A	ENSP00000447907.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 59454 AN: 150138 Hom.: 14096 Cov.: 29

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.396 AC: 59538 AN: 150256 Hom.: 14131 Cov.: 29 AF XY: 0.392 AC XY: 28751 AN XY: 73262

African (AFR) AF: 0.686 AC: 28205 AN: 41116

American (AMR) AF: 0.291 AC: 4368 AN: 15006

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1501 AN: 3458

East Asian (EAS) AF: 0.233 AC: 1149 AN: 4932

South Asian (SAS) AF: 0.285 AC: 1344 AN: 4718

European-Finnish (FIN) AF: 0.265 AC: 2736 AN: 10326

Middle Eastern (MID) AF: 0.361 AC: 99 AN: 274

European-Non Finnish (NFE) AF: 0.283 AC: 19098 AN: 67454

Other (OTH) AF: 0.352 AC: 729 AN: 2070

Alfa AF: 0.317 Hom.: 33171

Bravo AF: 0.407

Asia WGS AF: 0.302 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.43
PhyloP100		-0.23
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: rs540520; hg19: chr12-120911786;