NM_001077199.3:c.49C>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001077199.3(SREK1):​c.49C>T​(p.Pro17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,551,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SREK1
NM_001077199.3 missense

Scores

2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.029132426).
BS2
High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SREK1NM_001077199.3 linkc.49C>T p.Pro17Ser missense_variant Exon 1 of 12 ENST00000334121.11 NP_001070667.1 Q8WXA9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SREK1ENST00000334121.11 linkc.49C>T p.Pro17Ser missense_variant Exon 1 of 12 2 NM_001077199.3 ENSP00000334538.6 Q8WXA9-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152264
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
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
GnomAD3 exomes
AF:
0.0000454
AC:
7
AN:
154220
Hom.:
0
AF XY:
0.0000612
AC XY:
5
AN XY:
81660
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000642
Gnomad SAS 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:
0.0000121
AC:
17
AN:
1399300
Hom.:
0
Cov.:
30
AF XY:
0.0000101
AC XY:
7
AN XY:
690200
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000392
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000517
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152382
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74526
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000544
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.49C>T (p.P17S) alteration is located in exon 1 (coding exon 1) of the SREK1 gene. This alteration results from a C to T substitution at nucleotide position 49, causing the proline (P) at amino acid position 17 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
23
DANN
Benign
0.96
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.49
N
LIST_S2
Uncertain
0.88
D;T
M_CAP
Benign
0.0059
T
MetaRNN
Benign
0.029
T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
0.80
.;N
REVEL
Benign
0.070
Sift
Benign
0.064
.;T
Sift4G
Benign
0.89
T;T
Polyphen
0.0060
.;B
Vest4
0.16
MutPred
0.28
Gain of catalytic residue at P17 (P = 0.0387);Gain of catalytic residue at P17 (P = 0.0387);
MVP
0.24
MPC
1.4
ClinPred
0.24
T
GERP RS
3.9
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7
gMVP
0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780392285; hg19: chr5-65440253; API