1-29149192-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_005626.5(SRSF4):c.703C>T(p.Arg235Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,609,754 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
SRSF4
NM_005626.5 missense
NM_005626.5 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 5.78
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 Likely_benign. Variant got -3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, SRSF4
BS2
?
High AC in GnomAdExome4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SRSF4 | NM_005626.5 | c.703C>T | p.Arg235Trp | missense_variant | 6/6 | ENST00000373795.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SRSF4 | ENST00000373795.7 | c.703C>T | p.Arg235Trp | missense_variant | 6/6 | 1 | NM_005626.5 | P1 | |
SRSF4 | ENST00000466448.4 | c.613C>T | p.Arg205Trp | missense_variant | 5/5 | 3 | |||
SRSF4 | ENST00000634348.1 | n.6789C>T | non_coding_transcript_exon_variant | 7/7 | 5 | ||||
SRSF4 | ENST00000691479.1 | c.*910C>T | 3_prime_UTR_variant, NMD_transcript_variant | 10/10 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151860Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000365 AC: 9AN: 246382Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134186
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1457894Hom.: 0 Cov.: 35 AF XY: 0.00000965 AC XY: 7AN XY: 725358
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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 submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The c.703C>T (p.R235W) 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 703, causing the arginine (R) at amino acid position 235 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at