20-43460207-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006275.6(SRSF6):​c.556A>G​(p.Ser186Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,614,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

SRSF6
NM_006275.6 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.49
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.07240665).
BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRSF6NM_006275.6 linkc.556A>G p.Ser186Gly missense_variant Exon 4 of 6 ENST00000244020.5 NP_006266.2 Q13247-1
SRSF6NR_034009.2 linkn.962A>G non_coding_transcript_exon_variant Exon 5 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRSF6ENST00000244020.5 linkc.556A>G p.Ser186Gly missense_variant Exon 4 of 6 1 NM_006275.6 ENSP00000244020.3 Q13247-1
ENSG00000288000ENST00000657241.1 linkc.535A>G p.Ser179Gly missense_variant Exon 4 of 26 ENSP00000499734.1 A0A590UK80

Frequencies

GnomAD3 genomes
AF:
0.0000525
AC:
8
AN:
152246
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250692
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135818
show subpopulations
Gnomad AFR exome
AF:
0.000126
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461852
Hom.:
0
Cov.:
33
AF XY:
0.00000963
AC XY:
7
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152364
Hom.:
0
Cov.:
33
AF XY:
0.0000805
AC XY:
6
AN XY:
74514
show subpopulations
Gnomad4 AFR
AF:
0.000192
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000567
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.556A>G (p.S186G) alteration is located in exon 4 (coding exon 4) of the SRSF6 gene. This alteration results from a A to G substitution at nucleotide position 556, causing the serine (S) at amino acid position 186 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
Benign
0.097
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.022
T
Eigen
Benign
-0.12
Eigen_PC
Benign
0.069
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.58
T
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.072
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.67
N
REVEL
Benign
0.039
Sift
Benign
0.24
T
Sift4G
Benign
0.45
T
Polyphen
0.0010
B
Vest4
0.25
MVP
0.043
MPC
0.071
ClinPred
0.14
T
GERP RS
4.9
Varity_R
0.12
gMVP
0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199949963; hg19: chr20-42088847; API