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GeneBe

14-69771367-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001320214.2(SRSF5):c.725G>T(p.Arg242Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SRSF5
NM_001320214.2 missense

Scores

1
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15458766).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF5NM_001320214.2 linkuse as main transcriptc.725G>T p.Arg242Leu missense_variant 8/8 ENST00000557154.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF5ENST00000557154.6 linkuse as main transcriptc.725G>T p.Arg242Leu missense_variant 8/82 NM_001320214.2 P1Q13243-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

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 17, 2022The c.725G>T (p.R242L) alteration is located in exon 8 (coding exon 7) of the SRSF5 gene. This alteration results from a G to T substitution at nucleotide position 725, causing the arginine (R) at amino acid position 242 to be replaced by a leucine (L). 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
0.15
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
T;T;T;.
Eigen
Benign
-0.070
Eigen_PC
Benign
0.055
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Benign
0.0094
T
MetaRNN
Benign
0.15
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M;M;M;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-3.4
D;D;D;D
REVEL
Benign
0.10
Sift
Uncertain
0.0060
D;D;D;D
Sift4G
Uncertain
0.019
D;D;D;D
Polyphen
0.013
B;B;B;B
Vest4
0.28
MutPred
0.38
Gain of catalytic residue at R242 (P = 0.0118);Gain of catalytic residue at R242 (P = 0.0118);Gain of catalytic residue at R242 (P = 0.0118);.;
MVP
0.16
MPC
0.12
ClinPred
0.97
D
GERP RS
3.0
Varity_R
0.29
gMVP
0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-70238084; COSMIC: COSV53683077; COSMIC: COSV53683077; API