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GeneBe

1-29154726-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2

The NM_005626.5(SRSF4):c.548G>A(p.Arg183Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,886 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: not found (cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SRSF4
NM_005626.5 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.48
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 Likely_benign. Variant got -4 ACMG points.

PP2
Missense variant where missense usually causes diseases, SRSF4
BP4
Computational evidence support a benign effect (MetaRNN=0.34089592).
BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF4NM_005626.5 linkuse as main transcriptc.548G>A p.Arg183Gln missense_variant 4/6 ENST00000373795.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF4ENST00000373795.7 linkuse as main transcriptc.548G>A p.Arg183Gln missense_variant 4/61 NM_005626.5 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251456
Hom.:
0
AF XY:
0.00
AC XY:
0
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:
0.0000462
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461886
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000378

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 GeneticsDec 27, 2023The c.548G>A (p.R183Q) alteration is located in exon 4 (coding exon 4) of the SRSF4 gene. This alteration results from a G to A substitution at nucleotide position 548, causing the arginine (R) at amino acid position 183 to be replaced by a glutamine (Q). 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
Pathogenic
0.72
BayesDel_addAF
Benign
-0.049
T
BayesDel_noAF
Benign
-0.31
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;.
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
D;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.34
T;T
MetaSVM
Benign
-0.82
T
MutationAssessor
Uncertain
2.2
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-2.7
D;.
REVEL
Benign
0.12
Sift
Uncertain
0.0060
D;.
Sift4G
Uncertain
0.055
T;T
Polyphen
1.0
D;.
Vest4
0.54
MutPred
0.23
Gain of phosphorylation at Y185 (P = 0.1091);Gain of phosphorylation at Y185 (P = 0.1091);
MVP
0.37
MPC
0.37
ClinPred
0.88
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.50
gMVP
0.69

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: rs1307767331; hg19: chr1-29481238; API