Menu
GeneBe

20-43460597-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006275.6(SRSF6):c.673C>T(p.Arg225Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

SRSF6
NM_006275.6 missense, splice_region

Scores

2
8
9
Splicing: ADA: 0.0008548
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.365
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 -4 ACMG points.

BS2
High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF6NM_006275.6 linkuse as main transcriptc.673C>T p.Arg225Cys missense_variant, splice_region_variant 5/6 ENST00000244020.5
SRSF6NR_034009.2 linkuse as main transcriptn.1079C>T splice_region_variant, non_coding_transcript_exon_variant 6/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF6ENST00000244020.5 linkuse as main transcriptc.673C>T p.Arg225Cys missense_variant, splice_region_variant 5/61 NM_006275.6 P2Q13247-1

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152100
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251458
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1461864
Hom.:
0
Cov.:
36
AF XY:
0.0000289
AC XY:
21
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152100
Hom.:
0
Cov.:
33
AF XY:
0.0000673
AC XY:
5
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000381
Hom.:
0
Bravo
AF:
0.0000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000412
AC:
5

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 GeneticsFeb 15, 2023The c.673C>T (p.R225C) alteration is located in exon 5 (coding exon 5) of the SRSF6 gene. This alteration results from a C to T substitution at nucleotide position 673, causing the arginine (R) at amino acid position 225 to be replaced by a cysteine (C). 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
0.31
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.42
T
Eigen
Benign
-0.050
Eigen_PC
Benign
-0.074
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.57
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-5.1
D
REVEL
Benign
0.14
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.016
D
Polyphen
1.0
D
Vest4
0.69
MVP
0.17
MPC
0.10
ClinPred
0.52
D
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.50
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00085
dbscSNV1_RF
Benign
0.062
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

LitVar

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

Other links and lift over

dbSNP: rs371201183; hg19: chr20-42089237; COSMIC: COSV54827843; API