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GeneBe

20-43460202-G-A

Variant summary

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

The NM_006275.6(SRSF6):c.551G>A(p.Arg184His) variant causes a missense change. The variant allele was found at a frequency of 0.000334 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R184R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

SRSF6
NM_006275.6 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09
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=0.15403196).
BS2
High AC in GnomAd4 at 56 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF6NM_006275.6 linkuse as main transcriptc.551G>A p.Arg184His missense_variant 4/6 ENST00000244020.5
SRSF6NR_034009.2 linkuse as main transcriptn.957G>A non_coding_transcript_exon_variant 5/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF6ENST00000244020.5 linkuse as main transcriptc.551G>A p.Arg184His missense_variant 4/61 NM_006275.6 P2Q13247-1

Frequencies

GnomAD3 genomes
AF:
0.000368
AC:
56
AN:
152194
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000603
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000189
AC:
47
AN:
249196
Hom.:
0
AF XY:
0.000192
AC XY:
26
AN XY:
135330
show subpopulations
Gnomad AFR exome
AF:
0.000195
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000302
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000330
AC:
483
AN:
1461616
Hom.:
0
Cov.:
33
AF XY:
0.000318
AC XY:
231
AN XY:
727112
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000197
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.000400
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.000368
AC:
56
AN:
152194
Hom.:
0
Cov.:
33
AF XY:
0.000363
AC XY:
27
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.000338
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000603
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000261
Hom.:
0
Bravo
AF:
0.000280
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.000582
AC:
5
ExAC
AF:
0.000247
AC:
30
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

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 22, 2023The c.551G>A (p.R184H) alteration is located in exon 4 (coding exon 4) of the SRSF6 gene. This alteration results from a G to A substitution at nucleotide position 551, causing the arginine (R) at amino acid position 184 to be replaced by a histidine (H). 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
0.33
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.25
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.0080
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.2
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.13
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.045
D
Polyphen
0.99
D
Vest4
0.41
MVP
0.21
MPC
0.095
ClinPred
0.057
T
GERP RS
6.0
Varity_R
0.22
gMVP
0.46

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: rs147863077; hg19: chr20-42088842; COSMIC: COSV99719655; API