Variant 12-120469494-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003769.3(SRSF9):c.116G>C(p.Arg39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SRSF9
NM_003769.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.155

Variant links:

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]

SRSF9 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2844172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRSF9	NM_003769.3 linkuse as main transcript	c.116G>C	p.Arg39Pro	missense_variant	1/4	ENST00000229390.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRSF9	ENST00000229390.8 linkuse as main transcript	c.116G>C	p.Arg39Pro	missense_variant	1/4	1	NM_003769.3	P3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000425

AC:

AN:

235320

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128582

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000345

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449982

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721318

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2023

The c.116G>C (p.R39P) alteration is located in exon 1 (coding exon 1) of the SRSF9 gene. This alteration results from a G to C substitution at nucleotide position 116, causing the arginine (R) at amino acid position 39 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.34

Cadd

Uncertain

Dann

Uncertain

0.98

DEOGEN2

Benign

0.15

Eigen

Benign

-0.14

Eigen_PC

Benign

0.0041

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.17

Sift

Benign

0.22

Sift4G

Benign

0.19

Polyphen

0.0020

Vest4

0.55

MutPred

0.53

Gain of methylation at K36 (P = 0.0485);

MVP

0.25

MPC

1.5

ClinPred

0.87

GERP RS

4.4

Varity_R

0.59

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over