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GeneBe

17-76736844-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_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

2
1
15

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

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP2
Missense variant where missense usually causes diseases, SRSF2
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/exons MANE UniProt
SRSF2NM_001195427.2 linkuse as main transcriptc.317C>T p.Pro106Leu missense_variant 1/3 ENST00000359995.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF2ENST00000359995.10 linkuse as main transcriptc.317C>T p.Pro106Leu missense_variant 1/31 NM_001195427.2 P1Q01130-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152196
Hom.:
0
Cov.:
34
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:
22
AN:
230096
Hom.:
0
AF XY:
0.0000392
AC XY:
5
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:
27
AN:
1452746
Hom.:
0
Cov.:
31
AF XY:
0.00000970
AC XY:
7
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:
5
AN:
152196
Hom.:
0
Cov.:
34
AF XY:
0.0000538
AC XY:
4
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:
6
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 03, 2022The 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
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
28
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
D
M_CAP
Pathogenic
0.94
D
MetaRNN
Benign
0.17
T;T;T;T;T
MetaSVM
Benign
-0.58
T
MutationAssessor
Benign
1.4
L;L;L;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Pathogenic
0.92
D
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
T
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.

Other links and lift over

dbSNP: rs776880365; hg19: chr17-74732926; API