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GeneBe

1-29148528-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM1PM2PP2BP4_Moderate

The NM_005626.5(SRSF4):c.1367C>T(p.Ser456Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SRSF4
NM_005626.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.57
Variant links:
Genes affected
SRSF4 (HGNC:10786): (serine and arginine rich splicing factor 4) Enables RNA binding activity. Involved in negative regulation of mRNA splicing, via spliceosome. Located in nuclear speck. Biomarker of Down syndrome; acute myeloid leukemia; clear cell renal cell carcinoma; and colon adenocarcinoma. [provided by Alliance of Genome Resources, Apr 2022]

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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 SRSF4_HUMAN
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, SRSF4
BP4
Computational evidence support a benign effect (MetaRNN=0.14553893).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF4NM_005626.5 linkuse as main transcriptc.1367C>T p.Ser456Leu missense_variant 6/6 ENST00000373795.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF4ENST00000373795.7 linkuse as main transcriptc.1367C>T p.Ser456Leu missense_variant 6/61 NM_005626.5 P1
SRSF4ENST00000634348.1 linkuse as main transcriptn.7453C>T non_coding_transcript_exon_variant 7/75
SRSF4ENST00000691479.1 linkuse as main transcriptc.*1574C>T 3_prime_UTR_variant, NMD_transcript_variant 10/10

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
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 07, 2023The c.1367C>T (p.S456L) alteration is located in exon 6 (coding exon 6) of the SRSF4 gene. This alteration results from a C to T substitution at nucleotide position 1367, causing the serine (S) at amino acid position 456 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
0.10
BayesDel_addAF
Benign
-0.081
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.046
T
Eigen
Benign
-0.022
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.63
T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L
MutationTaster
Benign
1.0
D;N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.32
N
REVEL
Benign
0.14
Sift
Uncertain
0.017
D
Sift4G
Uncertain
0.0090
D
Polyphen
0.061
B
Vest4
0.15
MutPred
0.39
Loss of phosphorylation at S456 (P = 3e-04);
MVP
0.23
MPC
0.20
ClinPred
0.82
D
GERP RS
4.5
Varity_R
0.13
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: chr1-29475040; API