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GeneBe

1-29149192-G-A

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

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.78
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 -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
SRSF4NM_005626.5 linkuse as main transcriptc.703C>T p.Arg235Trp missense_variant 6/6 ENST00000373795.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF4ENST00000373795.7 linkuse as main transcriptc.703C>T p.Arg235Trp missense_variant 6/61 NM_005626.5 P1
SRSF4ENST00000466448.4 linkuse as main transcriptc.613C>T p.Arg205Trp missense_variant 5/53
SRSF4ENST00000634348.1 linkuse as main transcriptn.6789C>T non_coding_transcript_exon_variant 7/75
SRSF4ENST00000691479.1 linkuse as main transcriptc.*910C>T 3_prime_UTR_variant, NMD_transcript_variant 10/10

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151860
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000365
AC:
9
AN:
246382
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134186
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000507
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1457894
Hom.:
0
Cov.:
35
AF XY:
0.00000965
AC XY:
7
AN XY:
725358
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000198
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151860
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74178
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000101
Hom.:
0
Bravo
AF:
0.0000529
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

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 GeneticsSep 16, 2021The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.20
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.27
T;.
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.87
D;T
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.52
D;D
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.7
L;.
MutationTaster
Benign
0.86
D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-5.3
D;.
REVEL
Benign
0.23
Sift
Uncertain
0.0010
D;.
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;.
Vest4
0.48
MVP
0.30
MPC
0.62
ClinPred
0.87
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.51
gMVP
0.54

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: rs750608937; hg19: chr1-29475704; API