Menu
GeneBe

1-70221650-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001350605.2(SRSF11):c.14C>T(p.Thr5Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SRSF11
NM_001350605.2 missense

Scores

2
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.89
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13616729).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF11NM_001350605.2 linkuse as main transcriptc.14C>T p.Thr5Ile missense_variant 1/12 ENST00000370949.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF11ENST00000370949.2 linkuse as main transcriptc.14C>T p.Thr5Ile missense_variant 1/121 NM_001350605.2 P4Q05519-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000406
AC:
1
AN:
246054
Hom.:
0
AF XY:
0.00000748
AC XY:
1
AN XY:
133608
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000908
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1459152
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
725696
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

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 GeneticsJun 21, 2021The c.14C>T (p.T5I) alteration is located in exon 2 (coding exon 1) of the SRSF11 gene. This alteration results from a C to T substitution at nucleotide position 14, causing the threonine (T) at amino acid position 5 to be replaced by an isoleucine (I). 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
0.23
BayesDel_addAF
Benign
-0.056
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
25
DANN
Uncertain
1.0
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.84
T;T;D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;N;.
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-0.14
N;N;N
REVEL
Benign
0.036
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.019
D;D;D
Polyphen
0.089
.;B;.
Vest4
0.49
MutPred
0.28
Loss of glycosylation at T5 (P = 0.0022);Loss of glycosylation at T5 (P = 0.0022);Loss of glycosylation at T5 (P = 0.0022);
MVP
0.068
MPC
0.92
ClinPred
0.62
D
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.34
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: rs1558153803; hg19: chr1-70687333; API