Genetic Variant NM_003137.5:c.1438G>A (chr6-35869084-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003137.5(SRPK1):c.1438G>A(p.Val480Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SRPK1
NM_003137.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.977

Publications

0 publications found

Variant links:

Genes affected

SRPK1 (HGNC:11305): (SRSF protein kinase 1) This gene encodes a serine/arginine protein kinase specific for the SR (serine/arginine-rich domain) family of splicing factors. The protein localizes to the nucleus and the cytoplasm. It is thought to play a role in regulation of both constitutive and alternative splicing by regulating intracellular localization of splicing factors. Alternative splicing of this gene results in multiple transcript variants. Additional alternatively spliced transcript variants have been described for this gene, but their full length nature have not been determined.[provided by RefSeq, Jul 2010]

SRPK1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08988184).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003137.5. 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
	SRPK1	NM_003137.5	MANE Select	c.1438G>A	p.Val480Ile	missense	Exon 12 of 16	NP_003128.3
	SRPK1	NR_034069.2		n.1508G>A		non_coding_transcript_exon	Exon 12 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRPK1	ENST00000373825.7	TSL:1 MANE Select	c.1438G>A	p.Val480Ile	missense	Exon 12 of 16	ENSP00000362931.2	Q96SB4-2
SRPK1	ENST00000361690.7	TSL:1	c.1486G>A	p.Val496Ile	missense	Exon 12 of 16	ENSP00000354674.3	H3BLV9
SRPK1	ENST00000423325.6	TSL:2	c.1390G>A	p.Val464Ile	missense	Exon 12 of 16	ENSP00000391069.2	Q96SB4-4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249122

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461578

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.0000448

AC:

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111862

Other (OTH)

AF:

0.0000166

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

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

AF:

0.0000263

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41402

American (AMR)

AF:

0.000131

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.00000827

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.054

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.085

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0060

MetaRNN

Benign

0.090

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.27

PhyloP100

0.98

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.34

REVEL

Benign

0.070

Sift

Benign

0.20

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.075

MutPred

0.48

Gain of catalytic residue at P482 (P = 0.0919)

MVP

0.35

MPC

0.21

ClinPred

0.093

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.041

gMVP

0.31

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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