5-66144419-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001077199.3(SREK1):​c.43C>G​(p.Leu15Val) 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SREK1
NM_001077199.3 missense

Scores

2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0500
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14404008).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SREK1NM_001077199.3 linkc.43C>G p.Leu15Val 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.43C>G p.Leu15Val missense_variant Exon 1 of 12 2 NM_001077199.3 ENSP00000334538.6 Q8WXA9-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1399132
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
690122
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 09, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.43C>G (p.L15V) alteration is located in exon 1 (coding exon 1) of the SREK1 gene. This alteration results from a C to G substitution at nucleotide position 43, causing the leucine (L) at amino acid position 15 to be replaced by a valine (V). 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
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Uncertain
25
DANN
Benign
0.95
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.0045
FATHMM_MKL
Benign
0.41
N
LIST_S2
Uncertain
0.91
D;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
0.030
.;N
REVEL
Benign
0.043
Sift
Benign
0.38
.;T
Sift4G
Benign
0.36
T;T
Polyphen
0.57
.;P
Vest4
0.20
MutPred
0.30
Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP
0.22
MPC
2.1
ClinPred
0.99
D
GERP RS
4.7
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
3.8
gMVP
0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-65440247; API