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GeneBe

1-29154736-T-C

Variant summary

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

The NM_005626.5(SRSF4):c.538A>G(p.Arg180Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

SRSF4
NM_005626.5 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10
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=0.25951236).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF4NM_005626.5 linkuse as main transcriptc.538A>G p.Arg180Gly missense_variant 4/6 ENST00000373795.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF4ENST00000373795.7 linkuse as main transcriptc.538A>G p.Arg180Gly missense_variant 4/61 NM_005626.5 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 GeneticsFeb 27, 2023The c.538A>G (p.R180G) alteration is located in exon 4 (coding exon 4) of the SRSF4 gene. This alteration results from a A to G substitution at nucleotide position 538, causing the arginine (R) at amino acid position 180 to be replaced by a glycine (G). 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
0.73
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.14
T;.
Eigen
Uncertain
0.20
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.26
T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Uncertain
2.2
M;.
MutationTaster
Benign
0.97
D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-4.0
D;.
REVEL
Benign
0.15
Sift
Uncertain
0.0080
D;.
Sift4G
Uncertain
0.015
D;D
Polyphen
0.99
D;.
Vest4
0.38
MutPred
0.31
Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);
MVP
0.21
MPC
0.36
ClinPred
0.98
D
GERP RS
-0.18
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.40
gMVP
0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-29481248; API