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GeneBe

14-69771282-C-T

Variant summary

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

The NM_001320214.2(SRSF5):c.640C>T(p.Arg214Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 1,614,034 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 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

SRSF5
NM_001320214.2 missense

Scores

3
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.372
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.18357089).
BS2
High AC in GnomAd4 at 23 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF5NM_001320214.2 linkuse as main transcriptc.640C>T p.Arg214Trp missense_variant 8/8 ENST00000557154.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF5ENST00000557154.6 linkuse as main transcriptc.640C>T p.Arg214Trp missense_variant 8/82 NM_001320214.2 P1Q13243-1

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152054
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000328
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000179
AC:
45
AN:
251466
Hom.:
0
AF XY:
0.000184
AC XY:
25
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.000794
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000273
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000275
AC:
402
AN:
1461862
Hom.:
0
Cov.:
32
AF XY:
0.000276
AC XY:
201
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.000536
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.000333
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000223
Hom.:
0
Bravo
AF:
0.000181
TwinsUK
AF:
0.000809
AC:
3
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000222
AC:
27
EpiCase
AF:
0.000218
EpiControl
AF:
0.000178

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 06, 2023The c.640C>T (p.R214W) 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 640, causing the arginine (R) at amino acid position 214 to be replaced by a tryptophan (W). 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
0.43
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.35
T;T;T;.
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.18
T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.6
M;M;M;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-5.0
D;D;D;D
REVEL
Benign
0.17
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
0.93
P;P;P;D
Vest4
0.52
MVP
0.17
MPC
0.10
ClinPred
0.26
T
GERP RS
2.4
Varity_R
0.49
gMVP
0.45

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: rs201759888; hg19: chr14-70237999; COSMIC: COSV105086856; COSMIC: COSV105086856; API