dbSNP rs762641128: SRSF6:p.Arg77Ser (chr20-43458482-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006275.6(SRSF6):c.229C>A(p.Arg77Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000221 in 1,359,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R77G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

SRSF6
NM_006275.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3221208).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006275.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF6	NM_006275.6	MANE Select	c.229C>A	p.Arg77Ser	missense	Exon 2 of 6	NP_006266.2
	SRSF6	NR_034009.2		n.367C>A		non_coding_transcript_exon	Exon 2 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRSF6	ENST00000244020.5	TSL:1 MANE Select	c.229C>A	p.Arg77Ser	missense	Exon 2 of 6	ENSP00000244020.3	Q13247-1
ENSG00000288000	ENST00000657241.1		c.208C>A	p.Arg70Ser	missense	Exon 2 of 26	ENSP00000499734.1	A0A590UK80
SRSF6	ENST00000945325.1		c.229C>A	p.Arg77Ser	missense	Exon 2 of 6	ENSP00000615384.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000221

AC:

AN:

1359488

Hom.:

Cov.:

AF XY:

0.00000447

AC XY:

AN XY:

671006

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27398

American (AMR)

AF:

0.00

AC:

AN:

32254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24090

East Asian (EAS)

AF:

0.00

AC:

AN:

31150

South Asian (SAS)

AF:

0.00

AC:

AN:

76678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3984

European-Non Finnish (NFE)

AF:

0.00000281

AC:

AN:

1067392

Other (OTH)

AF:

0.00

AC:

AN:

56482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.023

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.5

PhyloP100

1.9

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.56

REVEL

Uncertain

0.31

Sift

Benign

0.71

Sift4G

Benign

0.49

Polyphen

0.059

Vest4

0.47

MutPred

0.46

Gain of phosphorylation at R77 (P = 0.0017)

MVP

0.67

MPC

1.7

ClinPred

0.59

GERP RS

3.5

PromoterAI

-0.034

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.72

Mutation Taster

=47/53

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over