Menu
GeneBe

14-69768861-C-A

Variant summary

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

The NM_001320214.2(SRSF5):c.261C>A(p.Asp87Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SRSF5
NM_001320214.2 missense

Scores

1
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.981
Variant links:
Genes affected
SRSF5 (HGNC:10787): (serine and arginine rich splicing factor 5) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

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=0.2025361).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF5NM_001320214.2 linkuse as main transcriptc.261C>A p.Asp87Glu missense_variant 4/8 ENST00000557154.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF5ENST00000557154.6 linkuse as main transcriptc.261C>A p.Asp87Glu missense_variant 4/82 NM_001320214.2 P1Q13243-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.000479
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
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:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152148
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.00
Gnomad4 OTH
AF:
0.000479
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 GeneticsAug 12, 2021The c.261C>A (p.D87E) alteration is located in exon 4 (coding exon 3) of the SRSF5 gene. This alteration results from a C to A substitution at nucleotide position 261, causing the aspartic acid (D) at amino acid position 87 to be replaced by a glutamic acid (E). 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
-0.017
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
18
DANN
Benign
0.93
DEOGEN2
Benign
0.044
T;T;T;.;T;.;T;.
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.27
FATHMM_MKL
Uncertain
0.79
D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.20
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.7
L;L;.;.;L;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.3
N;N;N;N;N;N;N;N
REVEL
Benign
0.072
Sift
Benign
0.18
T;T;T;T;T;T;T;T
Sift4G
Benign
0.39
T;T;T;T;T;T;T;T
Polyphen
0.50
P;P;.;.;P;P;.;.
Vest4
0.33
MutPred
0.28
Gain of catalytic residue at Y85 (P = 0.0891);Gain of catalytic residue at Y85 (P = 0.0891);Gain of catalytic residue at Y85 (P = 0.0891);Gain of catalytic residue at Y85 (P = 0.0891);Gain of catalytic residue at Y85 (P = 0.0891);.;Gain of catalytic residue at Y85 (P = 0.0891);Gain of catalytic residue at Y85 (P = 0.0891);
MVP
0.54
MPC
1.1
ClinPred
0.32
T
GERP RS
1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.075
gMVP
0.42

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: rs1467710301; hg19: chr14-70235578; API