GeneBe

rs780392285

Variant names:

Variant summary

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

The NM_001077199.3(SREK1):​c.49C>A​(p.Pro17Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. P17S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SREK1
NM_001077199.3 missense

Scores

2
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02

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]

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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=0.11466274).

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

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SREK1
NM_001077199.3
MANE Select
c.49C>Ap.Pro17Thr
missense
Exon 1 of 12NP_001070667.1Q8WXA9-2
SREK1
NM_001323529.2
c.49C>Ap.Pro17Thr
missense
Exon 1 of 12NP_001310458.1
SREK1
NM_001323533.2
c.49C>Ap.Pro17Thr
missense
Exon 1 of 11NP_001310462.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SREK1
ENST00000334121.11
TSL:2 MANE Select
c.49C>Ap.Pro17Thr
missense
Exon 1 of 12ENSP00000334538.6Q8WXA9-2
SREK1
ENST00000612404.4
TSL:1
c.49C>Ap.Pro17Thr
missense
Exon 1 of 3ENSP00000481430.1A0A087WY03
SREK1
ENST00000522912.5
TSL:1
n.49C>A
non_coding_transcript_exon
Exon 1 of 13ENSP00000427935.1E5RFV3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
154220
AF XY:
0.00
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
23
DANN
Benign
0.94
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.095
FATHMM_MKL
Benign
0.24
N
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.1
T
PhyloP100
2.0
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
0.50
N
REVEL
Benign
0.059
Sift
Benign
0.093
T
Sift4G
Benign
0.82
T
Polyphen
0.14
B
Vest4
0.20
MutPred
0.36
Gain of catalytic residue at P17 (P = 0.008)
MVP
0.17
MPC
1.4
ClinPred
0.98
D
GERP RS
3.9
PromoterAI
0.13
Neutral
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7
gMVP
0.68
Mutation Taster
=92/8
polymorphism

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

Other links and lift over

dbSNP: rs780392285; hg19: chr5-65440253; API