Variant 20-43461047-C-T details in Genebe, Genetics Data Aggregator

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

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]

SRSF6 links:

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
SRSF6	NM_006275.6 linkuse as main transcript	c.1019C>T	p.Ser340Leu	missense_variant	6/6	ENST00000244020.5
SRSF6	NR_034009.2 linkuse as main transcript	n.1425C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRSF6	ENST00000244020.5 linkuse as main transcript	c.1019C>T	p.Ser340Leu	missense_variant	6/6	1	NM_006275.6	P2	Q13247-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000893

AC:

AN:

223986

Hom.:

AF XY:

0.0000166

AC XY:

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:

AN:

1432186

Hom.:

Cov.:

AF XY:

0.00000845

AC XY:

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.:

Alfa

AF:

0.000398

Hom.:

ExAC

AF:

0.0000165

AC:

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 submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The 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

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.74

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.25

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0090

Polyphen

0.92

Vest4

0.65

MutPred

0.35

Loss of phosphorylation at S340 (P = 0);

MVP

0.14

MPC

0.069

ClinPred

0.84

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over