Menu
GeneBe

20-43461047-C-T

Variant summary

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

The NM_006275.6(SRSF6):c.1019C>T(p.Ser340Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000628 in 1,432,186 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

SRSF6
NM_006275.6 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.42
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 GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF6NM_006275.6 linkuse as main transcriptc.1019C>T p.Ser340Leu missense_variant 6/6 ENST00000244020.5
SRSF6NR_034009.2 linkuse as main transcriptn.1425C>T non_coding_transcript_exon_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF6ENST00000244020.5 linkuse as main transcriptc.1019C>T p.Ser340Leu missense_variant 6/61 NM_006275.6 P2Q13247-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000893
AC:
2
AN:
223986
Hom.:
0
AF XY:
0.0000166
AC XY:
2
AN XY:
120780
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000492
Gnomad NFE exome
AF:
0.00000959
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000628
AC:
9
AN:
1432186
Hom.:
0
Cov.:
33
AF XY:
0.00000845
AC XY:
6
AN XY:
710362
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:
0.0000245
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.00000455
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.000398
Hom.:
0
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 10, 2023The c.1019C>T (p.S340L) alteration is located in exon 6 (coding exon 6) of the SRSF6 gene. This alteration results from a C to T substitution at nucleotide position 1019, causing the serine (S) at amino acid position 340 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
Uncertain
0.54
BayesDel_addAF
Uncertain
0.040
T
BayesDel_noAF
Benign
-0.18
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
T
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.74
T
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.43
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.25
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0090
D
Polyphen
0.92
P
Vest4
0.65
MutPred
0.35
Loss of phosphorylation at S340 (P = 0);
MVP
0.14
MPC
0.069
ClinPred
0.84
D
GERP RS
5.8
Varity_R
0.65
gMVP
0.49

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: rs768696362; hg19: chr20-42089687; API