rs139360328

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003769.3(SRSF9):c.605G>A(p.Arg202His) variant causes a missense change. The variant allele was found at a frequency of 0.0000589 in 1,612,204 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 1 hom. )

Consequence

SRSF9
NM_003769.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.44

Publications

5 publications found

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:

GATC (HGNC:25068): (glutamyl-tRNA amidotransferase subunit C) Enables glutaminyl-tRNA synthase (glutamine-hydrolyzing) activity. Involved in glutaminyl-tRNAGln biosynthesis via transamidation and mitochondrial translation. Located in mitochondrion. Part of glutamyl-tRNA(Gln) amidotransferase complex. Implicated in combined oxidative phosphorylation deficiency 42. [provided by Alliance of Genome Resources, Apr 2022]

GATC Gene-Disease associations (from GenCC):

combined oxidative phosphorylation deficiency 42
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

GATC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06672776).

BS2

High AC in GnomAd4 at 17 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003769.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRSF9	NM_003769.3	MANE Select	c.605G>A	p.Arg202His	missense	Exon 4 of 4	NP_003760.1	Q13242
GATC	NM_176818.3	MANE Select	c.*2121C>T		3_prime_UTR	Exon 4 of 4	NP_789788.1	O43716
GATC	NR_033684.2		n.2667C>T		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRSF9	ENST00000229390.8	TSL:1 MANE Select	c.605G>A	p.Arg202His	missense	Exon 4 of 4	ENSP00000229390.3	Q13242
GATC	ENST00000551765.6	TSL:1 MANE Select	c.*2121C>T		3_prime_UTR	Exon 4 of 4	ENSP00000446872.1	O43716
SRSF9	ENST00000957766.1		c.605G>A	p.Arg202His	missense	Exon 4 of 5	ENSP00000627825.1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000796

AC:

AN:

251318

AF XY:

0.0000736

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000534

AC:

AN:

1460092

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

726362

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33410

American (AMR)

AF:

0.0000224

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000228

AC:

AN:

4388

European-Non Finnish (NFE)

AF:

0.0000504

AC:

AN:

1111920

Other (OTH)

AF:

0.0000996

AC:

AN:

60238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000112

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41494

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.551

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000143

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

-0.079

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.71

M_CAP

Benign

0.015

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

5.4

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.6

REVEL

Benign

0.17

Sift

Uncertain

0.010

Sift4G

Uncertain

0.013

Polyphen

0.027

Vest4

0.17

MVP

0.24

MPC

2.0

ClinPred

0.051

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.58

Mutation Taster

=68/32

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over