12-120473010-C-T

Variant names:

• chr12-120473010-C-T
• rs10849753
• ENST00000957767.1:c.-106+1626G>A

Variant summary

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

The NM_001037494.2(DYNLL1):​c.-7+2906C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,048 control chromosomes in the GnomAD database, including 5,981 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 0.26 (5981 hom., cov: 31)
• Consequence: DYNLL1 NM_001037494.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• Publications: 10 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037494.2. 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+2906C>T		intron	N/A	NP_001032583.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF9	ENST00000957767.1		c.-106+1626G>A		intron	N/A	ENSP00000627826.1
	SRSF9	ENST00000957768.1		c.-106+560G>A		intron	N/A	ENSP00000627827.1
	SRSF9	ENST00000706469.1		c.89+1626G>A		intron	N/A	ENSP00000516402.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39478 AN: 151930 Hom.: 5968 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.260 AC: 39502 AN: 152048 Hom.: 5981 Cov.: 31 AF XY: 0.264 AC XY: 19597 AN XY: 74318

African (AFR) AF: 0.110 AC: 4559 AN: 41474

American (AMR) AF: 0.274 AC: 4185 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 806 AN: 3468

East Asian (EAS) AF: 0.497 AC: 2566 AN: 5166

South Asian (SAS) AF: 0.300 AC: 1445 AN: 4810

European-Finnish (FIN) AF: 0.334 AC: 3528 AN: 10568

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21606 AN: 67968

Other (OTH) AF: 0.246 AC: 520 AN: 2112

Alfa AF: 0.288 Hom.: 8462

Bravo AF: 0.249

Asia WGS AF: 0.352 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.68
PhyloP100		0.49
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: rs10849753; hg19: chr12-120910813;