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GeneBe

1-29149155-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_005626.5(SRSF4):c.740G>A(p.Ser247Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,457,424 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: 0.0000021 ( 0 hom. )

Consequence

SRSF4
NM_005626.5 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12
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 1 ACMG points.

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=0.15942812).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF4NM_005626.5 linkuse as main transcriptc.740G>A p.Ser247Asn missense_variant 6/6 ENST00000373795.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF4ENST00000373795.7 linkuse as main transcriptc.740G>A p.Ser247Asn missense_variant 6/61 NM_005626.5 P1
SRSF4ENST00000466448.4 linkuse as main transcriptc.650G>A p.Ser217Asn missense_variant 5/53
SRSF4ENST00000634348.1 linkuse as main transcriptn.6826G>A non_coding_transcript_exon_variant 7/75
SRSF4ENST00000691479.1 linkuse as main transcriptc.*947G>A 3_prime_UTR_variant, NMD_transcript_variant 10/10

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250340
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135590
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:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1457424
Hom.:
0
Cov.:
35
AF XY:
0.00000276
AC XY:
2
AN XY:
725030
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

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 19, 2023The c.740G>A (p.S247N) alteration is located in exon 6 (coding exon 6) of the SRSF4 gene. This alteration results from a G to A substitution at nucleotide position 740, causing the serine (S) at amino acid position 247 to be replaced by an asparagine (N). 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
0.20
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T;.
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.74
T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.6
N;.
REVEL
Benign
0.036
Sift
Uncertain
0.0090
D;.
Sift4G
Uncertain
0.054
T;D
Polyphen
0.11
B;.
Vest4
0.40
MutPred
0.31
Loss of phosphorylation at S247 (P = 0);.;
MVP
0.28
MPC
0.30
ClinPred
0.49
T
GERP RS
5.8
Varity_R
0.13
gMVP
0.57

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: rs770452041; hg19: chr1-29475667; API