rs540520

Positions:

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

Variant summary

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

The NM_001037494.2(DYNLL1):​c.-7+3879G>A 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: DYNLL1 NM_001037494.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNLL1	NM_001037494.2	c.-7+3879G>A		intron_variant			NP_001032583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRSF9	ENST00000706469.1	c.89+653C>T		intron_variant				ENSP00000516402.1
DYNLL1	ENST00000392509.6	c.-7+3879G>A		intron_variant		3		ENSP00000376297.2
DYNLL1	ENST00000548342.5	c.-144+3879G>A		intron_variant		2		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

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.352

Alfa AF: 0.301 Hom.: 12530

Bravo AF: 0.407

Asia WGS AF: 0.302 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.43

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: rs540520; hg19: chr12-120911786;