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GeneBe

1-29150151-C-T

Variant summary

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

The NM_005626.5(SRSF4):c.620G>A(p.Arg207Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,778 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: 31)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

SRSF4
NM_005626.5 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.25
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]

Genome browser will be placed here

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=0.31910932).
BS2
High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF4NM_005626.5 linkuse as main transcriptc.620G>A p.Arg207Gln missense_variant 5/6 ENST00000373795.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF4ENST00000373795.7 linkuse as main transcriptc.620G>A p.Arg207Gln missense_variant 5/61 NM_005626.5 P1
SRSF4ENST00000466448.4 linkuse as main transcriptc.579-925G>A intron_variant 3
SRSF4ENST00000634348.1 linkuse as main transcriptn.6706G>A non_coding_transcript_exon_variant 6/75
SRSF4ENST00000691479.1 linkuse as main transcriptc.*827G>A 3_prime_UTR_variant, NMD_transcript_variant 9/10

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251426
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461778
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.0000113

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 GeneticsOct 10, 2023The c.620G>A (p.R207Q) alteration is located in exon 5 (coding exon 5) of the SRSF4 gene. This alteration results from a G to A substitution at nucleotide position 620, causing the arginine (R) at amino acid position 207 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
Benign
0.13
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.34
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.040
T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.32
T
MetaSVM
Benign
-0.77
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.17
Sift
Benign
0.12
T
Sift4G
Uncertain
0.010
D
Polyphen
1.0
D
Vest4
0.40
MutPred
0.32
Loss of methylation at R207 (P = 0.0345);
MVP
0.41
MPC
0.37
ClinPred
0.81
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.15
gMVP
0.53

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: rs1034723770; hg19: chr1-29476663; API