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GeneBe

17-58007068-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM5PP2

The NM_006924.5(SRSF1):c.70C>T(p.Pro24Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P24L) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Consequence

SRSF1
NM_006924.5 missense

Scores

4
4
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.93
Variant links:
Genes affected
SRSF1 (HGNC:10780): (serine and arginine rich splicing factor 1) This gene encodes a member of the arginine/serine-rich splicing factor protein family. The encoded protein can either activate or repress splicing, depending on its phosphorylation state and its interaction partners. Multiple transcript variants have been found for this gene. There is a pseudogene of this gene on chromosome 13. [provided by RefSeq, Jun 2014]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM1
In a domain RRM 1 (size 75) in uniprot entity SRSF1_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_006924.5
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr17-58007067-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1331676.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=1, Uncertain_significance=1}.
PP2
Missense variant where missense usually causes diseases, SRSF1

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF1NM_006924.5 linkuse as main transcriptc.70C>T p.Pro24Ser missense_variant 1/4 ENST00000258962.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF1ENST00000258962.5 linkuse as main transcriptc.70C>T p.Pro24Ser missense_variant 1/41 NM_006924.5 P1Q07955-1
ENST00000624641.2 linkuse as main transcriptn.417G>A non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Autism spectrum disorder Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingDepartment of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized MedicineAug 16, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Uncertain
0.082
D
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
30
DANN
Uncertain
0.98
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Uncertain
0.94
D
M_CAP
Benign
0.010
T
MetaRNN
Uncertain
0.57
D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.53
N;.;.;N
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.85
D
Sift4G
Benign
0.094
T;T;T;T
Polyphen
1.0
.;.;.;D
Vest4
0.70
MutPred
0.60
Loss of catalytic residue at P24 (P = 0.0407);Loss of catalytic residue at P24 (P = 0.0407);Loss of catalytic residue at P24 (P = 0.0407);Loss of catalytic residue at P24 (P = 0.0407);
MVP
0.50
MPC
3.2
ClinPred
1.0
D
GERP RS
6.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8
Varity_R
0.91
gMVP
0.97

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr17-56084429; API