17-76736844-G-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_001195427.2(SRSF2):c.317C>T(p.Pro106Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000199 in 1,604,942 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: 34)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SRSF2
NM_001195427.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.41

Variant links:

Genes affected

SRSF2 (HGNC:10783): (serine and arginine rich splicing factor 2) 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 transcript variants encoding the same protein and one non-coding transcript variant have been found for this gene. In addition, a pseudogene of this gene has been found on chromosome 11. [provided by RefSeq, Sep 2010]

SRSF2 links:

MFSD11 (HGNC:25458): (major facilitator superfamily domain containing 11) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD11 links:

ENSG00000267168 (HGNC:):

ENSG00000267168 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17154789).

BS2

High AC in GnomAd4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF2	NM_001195427.2 link	c.317C>T	p.Pro106Leu	missense_variant	Exon 1 of 3	ENST00000359995.10	NP_001182356.1	Q01130-1A0A024R8U5Q53FN0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF2	ENST00000359995.10 link	c.317C>T	p.Pro106Leu	missense_variant	Exon 1 of 3	1	NM_001195427.2	ENSP00000353089.5		Q01130-1
ENSG00000267168	ENST00000587459.1 link	c.239-1438G>A		intron_variant	Intron 1 of 1	5		ENSP00000466829.1		K7EN84

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000479

GnomAD3 exomes

AF:

0.0000956

AC:

AN:

230096

Hom.:

AF XY:

0.0000392

AC XY:

AN XY:

127686

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000648

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1452746

Hom.:

Cov.:

AF XY:

0.00000970

AC XY:

AN XY:

722008

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000607

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

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:

0.000479

Bravo

AF:

0.0000416

ExAC

AF:

0.0000512

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.317C>T (p.P106L) alteration is located in exon 1 (coding exon 1) of the SRSF2 gene. This alteration results from a C to T substitution at nucleotide position 317, causing the proline (P) at amino acid position 106 to be replaced by a leucine (L). 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

0.16

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.13

T;T;.;.;T

Eigen

Benign

0.0023

Eigen_PC

Benign

0.040

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.76

.;.;T;T;D

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.17

T;T;T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.4

L;L;L;.;.

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.2

N;.;.;.;.

REVEL

Benign

0.12

Sift

Uncertain

0.0040

D;.;.;.;.

Sift4G

Benign

0.30

T;T;T;T;.

Polyphen

0.64

P;P;.;.;.

Vest4

0.27

MutPred

0.26

Loss of glycosylation at P106 (P = 0.0075);Loss of glycosylation at P106 (P = 0.0075);Loss of glycosylation at P106 (P = 0.0075);Loss of glycosylation at P106 (P = 0.0075);Loss of glycosylation at P106 (P = 0.0075);

MVP

0.50

MPC

1.5

ClinPred

0.16

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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