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GeneBe

14-69771255-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001320214.2(SRSF5):c.613C>T(p.Arg205Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,613,974 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R205H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 1 hom. )

Consequence

SRSF5
NM_001320214.2 missense

Scores

5
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.87
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 -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.3274582).
BS2
High AC in GnomAdExome4 at 42 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF5NM_001320214.2 linkuse as main transcriptc.613C>T p.Arg205Cys missense_variant 8/8 ENST00000557154.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF5ENST00000557154.6 linkuse as main transcriptc.613C>T p.Arg205Cys missense_variant 8/82 NM_001320214.2 P1Q13243-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152088
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000865
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
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251476
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000298
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000287
AC:
42
AN:
1461886
Hom.:
1
Cov.:
32
AF XY:
0.0000316
AC XY:
23
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.000689
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152088
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74252
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000865
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
Alfa
AF:
0.0000847
Hom.:
0
Bravo
AF:
0.0000302
EpiCase
AF:
0.000109
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 GeneticsJun 07, 2022The c.613C>T (p.R205C) alteration is located in exon 8 (coding exon 7) of the SRSF5 gene. This alteration results from a C to T substitution at nucleotide position 613, causing the arginine (R) at amino acid position 205 to be replaced by a cysteine (C). 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
0.39
BayesDel_addAF
Uncertain
0.016
T
BayesDel_noAF
Benign
-0.21
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
T;T;T;.
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.33
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.8
M;M;M;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-4.9
D;D;D;D
REVEL
Uncertain
0.32
Sift
Benign
0.061
T;T;T;T
Sift4G
Uncertain
0.0080
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.51
MutPred
0.43
Gain of catalytic residue at R205 (P = 0.0055);Gain of catalytic residue at R205 (P = 0.0055);Gain of catalytic residue at R205 (P = 0.0055);.;
MVP
0.32
MPC
0.13
ClinPred
0.81
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.21
gMVP
0.52

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: rs1332582034; hg19: chr14-70237972; COSMIC: COSV53683511; COSMIC: COSV53683511; API