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GeneBe

1-70228549-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001350605.2(SRSF11):c.331G>A(p.Ala111Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,460,436 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SRSF11
NM_001350605.2 missense

Scores

3
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0
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 Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF11NM_001350605.2 linkuse as main transcriptc.331G>A p.Ala111Thr missense_variant 2/12 ENST00000370949.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF11ENST00000370949.2 linkuse as main transcriptc.331G>A p.Ala111Thr missense_variant 2/121 NM_001350605.2 P4Q05519-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250138
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135200
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:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1460436
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
726514
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:
0.0000171
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2

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 GeneticsFeb 28, 2024The c.331G>A (p.A111T) alteration is located in exon 3 (coding exon 2) of the SRSF11 gene. This alteration results from a G to A substitution at nucleotide position 331, causing the alanine (A) at amino acid position 111 to be replaced by a threonine (T). 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
Uncertain
0.46
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
32
DANN
Uncertain
1.0
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;D;D
M_CAP
Benign
0.0056
T
MetaRNN
Uncertain
0.43
T;T;T
MetaSVM
Benign
-0.67
T
MutationAssessor
Benign
1.5
L;L;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-1.7
N;N;N
REVEL
Uncertain
0.42
Sift
Benign
0.057
T;T;T
Sift4G
Benign
0.24
T;T;T
Polyphen
0.99
.;D;.
Vest4
0.67
MVP
0.35
MPC
0.82
ClinPred
0.55
D
GERP RS
5.3
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.27
gMVP
0.80

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.

Other links and lift over

dbSNP: rs375568012; hg19: chr1-70694232; API