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GeneBe

17-58007019-C-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PP2PP3_StrongPP5_Moderate

The NM_006924.5(SRSF1):c.119G>T(p.Gly40Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SRSF1
NM_006924.5 missense

Scores

9
2
3

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 7.06
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 Pathogenic. Variant got 11 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;
PP2
Missense variant where missense usually causes diseases, SRSF1
PP3
MetaRNN computational evidence supports a deleterious effect, 0.968
PP5
Variant 17-58007019-C-A is Pathogenic according to our data. Variant chr17-58007019-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 2429786.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-58007019-C-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF1NM_006924.5 linkuse as main transcriptc.119G>T p.Gly40Val missense_variant 1/4 ENST00000258962.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF1ENST00000258962.5 linkuse as main transcriptc.119G>T p.Gly40Val missense_variant 1/41 NM_006924.5 P1Q07955-1
ENST00000624641.2 linkuse as main transcriptn.368C>A non_coding_transcript_exon_variant 1/1

Frequencies

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

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Intellectual disability;C4022738:Neurodevelopmental delay Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingEquipe Genetique des Anomalies du Developpement, Université de BourgogneFeb 15, 2023- -
Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMAug 29, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
31
DANN
Benign
0.97
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
1.0
FATHMM_MKL
Uncertain
0.94
D
M_CAP
Benign
0.027
D
MetaRNN
Pathogenic
0.97
D;D;D;D
MetaSVM
Uncertain
0.30
D
MutationAssessor
Pathogenic
4.4
H;.;.;H
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.88
D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
.;.;.;D
Vest4
0.94
MutPred
0.87
Loss of ubiquitination at K38 (P = 0.0714);Loss of ubiquitination at K38 (P = 0.0714);Loss of ubiquitination at K38 (P = 0.0714);Loss of ubiquitination at K38 (P = 0.0714);
MVP
0.83
MPC
3.7
ClinPred
1.0
D
GERP RS
6.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.96
gMVP
1.0

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: chr17-56084380; API