Genetic Variant SREK1:p.Arg342Cys (chr5-66170073-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001077199.3(SREK1):c.1024C>T(p.Arg342Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,606,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000089 ( 0 hom. )

Consequence

SREK1
NM_001077199.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

Publications

0 publications found

Variant links:

Genes affected

SREK1 (HGNC:17882): (splicing regulatory glutamic acid and lysine rich protein 1) This gene encodes a member of a family of serine/arginine-rich (SR) splicing proteins containing RNA recognition motif (RRM) domains. The encoded protein interacts with other SR proteins to modulate splice site selection. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

SREK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12664717).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077199.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SREK1	NM_001077199.3	MANE Select	c.1024C>T	p.Arg342Cys	missense	Exon 8 of 12	NP_001070667.1	Q8WXA9-2
SREK1	NM_001323529.2		c.1024C>T	p.Arg342Cys	missense	Exon 8 of 12	NP_001310458.1
SREK1	NM_001323533.2		c.1024C>T	p.Arg342Cys	missense	Exon 8 of 11	NP_001310462.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SREK1	ENST00000334121.11	TSL:2 MANE Select	c.1024C>T	p.Arg342Cys	missense	Exon 8 of 12	ENSP00000334538.6	Q8WXA9-2
SREK1	ENST00000380918.7	TSL:1	c.676C>T	p.Arg226Cys	missense	Exon 9 of 13	ENSP00000370305.3	Q8WXA9-1
SREK1	ENST00000284041.7	TSL:1	n.957C>T		non_coding_transcript_exon	Exon 8 of 12

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000123

AC:

AN:

244820

AF XY:

0.00000755

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000906

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000894

AC:

AN:

1454666

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

723330

show subpopulations

African (AFR)

AF:

0.000181

AC:

AN:

33116

American (AMR)

AF:

0.00

AC:

AN:

43944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25910

East Asian (EAS)

AF:

0.00

AC:

AN:

39480

South Asian (SAS)

AF:

0.00

AC:

AN:

84740

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53168

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00000451

AC:

AN:

1108506

Other (OTH)

AF:

0.0000166

AC:

AN:

60064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

151968

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.0000967

AC:

AN:

41372

American (AMR)

AF:

0.00

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000945

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

0.18

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Benign

-0.055

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0094

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

1.2

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.065

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.025

Polyphen

0.010

Vest4

0.30

MVP

0.10

MPC

0.39

ClinPred

0.58

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.30

Mutation Taster

=84/16

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over