chr5-64728179-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_173829.4(SREK1IP1):c.206G>A(p.Arg69Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000016 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SREK1IP1
NM_173829.4 missense, splice_region
NM_173829.4 missense, splice_region
Scores
1
18
Splicing: ADA: 0.001405
2
Clinical Significance
Conservation
PhyloP100: 0.164
Genes affected
SREK1IP1 (HGNC:26716): (SREK1 interacting protein 1) Predicted to enable nucleic acid binding activity and zinc ion binding activity. Predicted to be involved in RNA splicing and mRNA processing. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0429022).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SREK1IP1 | NM_173829.4 | c.206G>A | p.Arg69Lys | missense_variant, splice_region_variant | 4/5 | ENST00000513458.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SREK1IP1 | ENST00000513458.9 | c.206G>A | p.Arg69Lys | missense_variant, splice_region_variant | 4/5 | 1 | NM_173829.4 | P1 | |
SREK1IP1 | ENST00000495198.6 | n.308G>A | splice_region_variant, non_coding_transcript_exon_variant | 4/4 | 3 | ||||
SREK1IP1 | ENST00000651194.1 | n.1066G>A | splice_region_variant, non_coding_transcript_exon_variant | 2/3 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 2AN: 139184Hom.: 0 Cov.: 31 FAILED QC
GnomAD3 genomes
?
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FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000162 AC: 2AN: 1230866Hom.: 0 Cov.: 30 AF XY: 0.00000165 AC XY: 1AN XY: 606106
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0000144 AC: 2AN: 139184Hom.: 0 Cov.: 31 AF XY: 0.0000298 AC XY: 2AN XY: 67040
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?
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2023 | The c.206G>A (p.R69K) alteration is located in exon 4 (coding exon 4) of the SREK1IP1 gene. This alteration results from a G to A substitution at nucleotide position 206, causing the arginine (R) at amino acid position 69 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of methylation at R69 (P = 0.0157);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at