rs762641128

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006275.6(SRSF6):​c.229C>A​(p.Arg77Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000221 in 1,359,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R77C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

SRSF6
NM_006275.6 missense

Scores

3
2
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92
Variant links:
Genes affected
SRSF6 (HGNC:10788): (serine and arginine rich splicing factor 6) The protein encoded by this gene is involved in mRNA splicing and may play a role in the determination of alternative splicing. The encoded nuclear protein belongs to the splicing factor SR family and has been shown to bind with and modulate another member of the family, SFRS12. Alternative splicing results in multiple transcript variants. In addition, two pseudogenes, one on chromosome 17 and the other on the X chromosome, have been found for this gene.[provided by RefSeq, Sep 2010]

Genome browser will be placed here

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;
BP4
Computational evidence support a benign effect (MetaRNN=0.3221208).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRSF6NM_006275.6 linkc.229C>A p.Arg77Ser missense_variant Exon 2 of 6 ENST00000244020.5 NP_006266.2 Q13247-1
SRSF6XM_047440372.1 linkc.229C>A p.Arg77Ser missense_variant Exon 2 of 3 XP_047296328.1
SRSF6NR_034009.2 linkn.367C>A non_coding_transcript_exon_variant Exon 2 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRSF6ENST00000244020.5 linkc.229C>A p.Arg77Ser missense_variant Exon 2 of 6 1 NM_006275.6 ENSP00000244020.3 Q13247-1
ENSG00000288000ENST00000657241.1 linkc.208C>A p.Arg70Ser missense_variant Exon 2 of 26 ENSP00000499734.1 A0A590UK80

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000221
AC:
3
AN:
1359488
Hom.:
0
Cov.:
33
AF XY:
0.00000447
AC XY:
3
AN XY:
671006
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000281
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Uncertain
0.035
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
23
DANN
Benign
0.97
DEOGEN2
Benign
0.023
T
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.84
T
M_CAP
Pathogenic
0.76
D
MetaRNN
Benign
0.32
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.5
L
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.56
N
REVEL
Uncertain
0.31
Sift
Benign
0.71
T
Sift4G
Benign
0.49
T
Polyphen
0.059
B
Vest4
0.47
MutPred
0.46
Gain of phosphorylation at R77 (P = 0.0017);
MVP
0.67
MPC
1.7
ClinPred
0.59
D
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.20
gMVP
0.72

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: chr20-42087122; API