rs606443

Positions:

• chr12-120472827-C-A
• chr12-120472827-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000706469.1(SRSF9):​c.89+1809G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,070 control chromosomes in the GnomAD database, including 41,496 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 0.73 (41496 hom., cov: 31)
• Consequence: SRSF9 ENST00000706469.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNLL1	NM_001037494.2	c.-7+2723C>A		intron_variant			NP_001032583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNLL1	ENST00000392509.6	c.-7+2723C>A		intron_variant		3		ENSP00000376297	P1
DYNLL1	ENST00000548342.5	c.-144+2723C>A		intron_variant		2		ENSP00000447907	P1
DYNLL1	ENST00000549649.5	c.-421+2723C>A		intron_variant		3		ENSP00000448834

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110692 AN: 151952 Hom.: 41442 Cov.: 31

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.729 AC: 110804 AN: 152070 Hom.: 41496 Cov.: 31 AF XY: 0.729 AC XY: 54141 AN XY: 74310

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.659

Alfa AF: 0.683 Hom.: 16299

Bravo AF: 0.727

Asia WGS AF: 0.710 AC: 2471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.8
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs606443; hg19: chr12-120910630;