12-120474407-G-A

Variant names:

• chr12-120474407-G-A
• rs17431717
• ENST00000706469.1:c.89+229C>T

Variant summary

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

The ENST00000706469.1(SRSF9):​c.89+229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 149,458 control chromosomes in the GnomAD database, including 2,437 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 0.17 (2437 hom., cov: 29)
• Consequence: SRSF9 ENST00000706469.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.461
• Publications: 6 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 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+4303G>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+229C>T		intron	N/A	ENSP00000516402.1
	DYNLL1	ENST00000392509.6	TSL:3	c.-7+4303G>A		intron	N/A	ENSP00000376297.2
	DYNLL1	ENST00000548342.5	TSL:2	c.-144+4303G>A		intron	N/A	ENSP00000447907.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 25646 AN: 149344 Hom.: 2438 Cov.: 29

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.0376

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.172 AC: 25657 AN: 149458 Hom.: 2437 Cov.: 29 AF XY: 0.168 AC XY: 12254 AN XY: 72742

African (AFR) AF: 0.218 AC: 8793 AN: 40308

American (AMR) AF: 0.120 AC: 1793 AN: 14994

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1253 AN: 3466

East Asian (EAS) AF: 0.0375 AC: 190 AN: 5062

South Asian (SAS) AF: 0.128 AC: 610 AN: 4764

European-Finnish (FIN) AF: 0.120 AC: 1187 AN: 9892

Middle Eastern (MID) AF: 0.247 AC: 71 AN: 288

European-Non Finnish (NFE) AF: 0.165 AC: 11142 AN: 67698

Other (OTH) AF: 0.178 AC: 370 AN: 2078

Alfa AF: 0.174 Hom.: 398

Bravo AF: 0.175

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		0.46
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: rs17431717; hg19: chr12-120912210;