Genetic Variant SRSF6:p.Pro281Pro (chr20-43460871-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006275.6(SRSF6):c.843T>C(p.Pro281Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 1,614,018 control chromosomes in the GnomAD database, including 595,363 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.88 ( 59672 hom., cov: 30)

Exomes 𝑓: 0.85 ( 535691 hom. )

Consequence

SRSF6
NM_006275.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0130

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:

ENSG00000288000 (HGNC:):

ENSG00000288000 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=-0.013 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF6	NM_006275.6 link	c.843T>C	p.Pro281Pro	synonymous_variant	Exon 6 of 6	ENST00000244020.5	NP_006266.2	Q13247-1
SRSF6	NR_034009.2 link	n.1249T>C		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF6	ENST00000244020.5 link	c.843T>C	p.Pro281Pro	synonymous_variant	Exon 6 of 6	1	NM_006275.6	ENSP00000244020.3		Q13247-1
ENSG00000288000	ENST00000657241.1 link	c.653+273T>C		intron_variant	Intron 5 of 25			ENSP00000499734.1		A0A590UK80

Frequencies

GnomAD3 genomes

AF:

0.882

AC:

134157

AN:

152022

Hom.:

59598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.963

Gnomad AMI

AF:

0.898

Gnomad AMR

AF:

0.909

Gnomad ASJ

AF:

0.802

Gnomad EAS

AF:

0.701

Gnomad SAS

AF:

0.648

Gnomad FIN

AF:

0.845

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.869

Gnomad OTH

AF:

0.866

GnomAD3 exomes

AF:

0.840

AC:

211123

AN:

251426

Hom.:

89816

AF XY:

0.826

AC XY:

112231

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.966

Gnomad AMR exome

AF:

0.936

Gnomad ASJ exome

AF:

0.801

Gnomad EAS exome

AF:

0.697

Gnomad SAS exome

AF:

0.647

Gnomad FIN exome

AF:

0.850

Gnomad NFE exome

AF:

0.869

Gnomad OTH exome

AF:

0.843

GnomAD4 exome

AF:

0.854

AC:

1247821

AN:

1461878

Hom.:

535691

Cov.:

AF XY:

0.846

AC XY:

615585

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.966

Gnomad4 AMR exome

AF:

0.933

Gnomad4 ASJ exome

AF:

0.799

Gnomad4 EAS exome

AF:

0.741

Gnomad4 SAS exome

AF:

0.651

Gnomad4 FIN exome

AF:

0.846

Gnomad4 NFE exome

AF:

0.869

Gnomad4 OTH exome

AF:

0.843

GnomAD4 genome

AF:

0.883

AC:

134292

AN:

152140

Hom.:

59672

Cov.:

AF XY:

0.876

AC XY:

65121

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.963

Gnomad4 AMR

AF:

0.909

Gnomad4 ASJ

AF:

0.802

Gnomad4 EAS

AF:

0.701

Gnomad4 SAS

AF:

0.648

Gnomad4 FIN

AF:

0.845

Gnomad4 NFE

AF:

0.869

Gnomad4 OTH

AF:

0.868

Alfa

AF:

0.868

Hom.:

64009

Bravo

AF:

0.895

Asia WGS

AF:

0.715

AC:

2487

AN:

3478

EpiCase

AF:

0.856

EpiControl

AF:

0.856

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.0

DANN

Benign

0.65

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over