Genetic Variant SRSF11:p.Arg393Gln (chr1-70250424-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001350605.2(SRSF11):c.1178G>A(p.Arg393Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000615 in 1,594,096 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: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

SRSF11
NM_001350605.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.07

Variant links:

Genes affected

SRSF11 (HGNC:10782): (serine and arginine rich splicing factor 11) This gene encodes 54-kD nuclear protein that contains an arginine/serine-rich region similar to segments found in pre-mRNA splicing factors. Although the function of this protein is not yet known, structure and immunolocalization data suggest that it may play a role in pre-mRNA processing. Alternative splicing results in multiple transcript variants encoding different proteins. In addition, a pseudogene of this gene has been found on chromosome 12.[provided by RefSeq, Sep 2010]

SRSF11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20052594).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF11	NM_001350605.2 link	c.1178G>A	p.Arg393Gln	missense_variant	Exon 11 of 12	ENST00000370949.2	NP_001337534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF11	ENST00000370949.2 link	c.1178G>A	p.Arg393Gln	missense_variant	Exon 11 of 12	1	NM_001350605.2	ENSP00000359987.2		Q05519-1Q5T757

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000403

AC:

AN:

248410

Hom.:

AF XY:

0.0000372

AC XY:

AN XY:

134558

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000631

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000645

AC:

AN:

1441986

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

718836

show subpopulations

Gnomad4 AFR exome

AF:

0.0000909

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000768

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1178G>A (p.R393Q) alteration is located in exon 12 (coding exon 11) of the SRSF11 gene. This alteration results from a G to A substitution at nucleotide position 1178, causing the arginine (R) at amino acid position 393 to be replaced by a glutamine (Q). 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

Benign

0.18

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.7

L;L;.

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.18

Sift

Uncertain

0.027

D;D;D

Sift4G

Benign

0.084

T;T;T

Polyphen

0.30, 0.81

.;B;P

Vest4

0.46

MVP

0.68

MPC

0.98

ClinPred

0.16

GERP RS

5.3

Varity_R

0.16

gMVP

0.20

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

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