Menu
GeneBe

14-69771322-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_001320214.2(SRSF5):c.680C>G(p.Ser227Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,920 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SRSF5
NM_001320214.2 missense

Scores

4
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31
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 Uncertain_significance. Variant got 3 ACMG points.

PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity SRSF5_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39901948).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF5NM_001320214.2 linkuse as main transcriptc.680C>G p.Ser227Cys missense_variant 8/8 ENST00000557154.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF5ENST00000557154.6 linkuse as main transcriptc.680C>G p.Ser227Cys missense_variant 8/82 NM_001320214.2 P1Q13243-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152078
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251458
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135906
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461842
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
727228
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:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152078
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74248
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000508
Hom.:
0
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

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 GeneticsSep 20, 2022The c.680C>G (p.S227C) alteration is located in exon 8 (coding exon 7) of the SRSF5 gene. This alteration results from a C to G substitution at nucleotide position 680, causing the serine (S) at amino acid position 227 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
Benign
0.25
BayesDel_addAF
Uncertain
0.058
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.32
T;T;T;.
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.40
T;T;T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
1.9
L;L;L;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-3.9
D;D;D;D
REVEL
Uncertain
0.39
Sift
Uncertain
0.0090
D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.47
MVP
0.41
MPC
0.14
ClinPred
0.66
D
GERP RS
5.9
Varity_R
0.29
gMVP
0.54

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: rs371196399; hg19: chr14-70238039; API