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GeneBe

6-36596796-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_003017.5(SRSF3):c.34G>C(p.Val12Leu) 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 (★).

Frequency

Genomes: not found (cov: 31)

Consequence

SRSF3
NM_003017.5 missense

Scores

3
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0
Variant links:
Genes affected
SRSF3 (HGNC:10785): (serine and arginine rich splicing factor 3) The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Two transcript variants, one protein-coding and the other non-coding, have been found for this gene. [provided by RefSeq, Sep 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, SRSF3

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF3NM_003017.5 linkuse as main transcriptc.34G>C p.Val12Leu missense_variant 2/6 ENST00000373715.11
SRSF3NR_036610.2 linkuse as main transcriptn.156G>C non_coding_transcript_exon_variant 2/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF3ENST00000373715.11 linkuse as main transcriptc.34G>C p.Val12Leu missense_variant 2/61 NM_003017.5 P1P84103-1

Frequencies

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

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 GeneticsDec 02, 2021The c.34G>C (p.V12L) alteration is located in exon 2 (coding exon 1) of the SRSF3 gene. This alteration results from a G to C substitution at nucleotide position 34, causing the valine (V) at amino acid position 12 to be replaced by a leucine (L). 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
0.96
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.38
T;T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.74
D;D
MetaSVM
Benign
-0.63
T
MutationAssessor
Benign
0.76
N;N
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.93
D
PROVEAN
Uncertain
-2.9
D;.
REVEL
Uncertain
0.45
Sift
Benign
0.099
T;.
Sift4G
Benign
0.062
T;T
Polyphen
0.94
P;P
Vest4
0.74
MutPred
0.48
Loss of catalytic residue at V12 (P = 0.0645);Loss of catalytic residue at V12 (P = 0.0645);
MVP
0.88
MPC
2.9
ClinPred
0.99
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.74
gMVP
0.82

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: chr6-36564573; API