Variant 3-38198769-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4BS2

The NM_005109.3(OXSR1):c.340A>G(p.Lys114Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,932 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: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

OXSR1
NM_005109.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.90

Variant links:

Genes affected

OXSR1 (HGNC:8508): (oxidative stress responsive kinase 1) The product of this gene belongs to the Ser/Thr protein kinase family of proteins. It regulates downstream kinases in response to environmental stress, and may play a role in regulating the actin cytoskeleton. [provided by RefSeq, Jul 2008]

OXSR1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26869386).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXSR1	NM_005109.3 link	c.340A>G	p.Lys114Glu	missense_variant	4/18	ENST00000311806.8	NP_005100.1	O95747

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OXSR1	ENST00000311806.8 link	c.340A>G	p.Lys114Glu	missense_variant	4/18	1	NM_005109.3	ENSP00000311713.3	O95747
OXSR1	ENST00000426620.5 link	n.*135A>G		non_coding_transcript_exon_variant	5/11	1		ENSP00000398356.1	F8WBK9
OXSR1	ENST00000426620.5 link	n.*135A>G		3_prime_UTR_variant	5/11	1		ENSP00000398356.1	F8WBK9
OXSR1	ENST00000446845.5 link	c.340A>G	p.Lys114Glu	missense_variant	4/15	5		ENSP00000415851.1	C9JIG9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460932

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726816

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 28, 2024

The c.340A>G (p.K114E) alteration is located in exon 4 (coding exon 4) of the OXSR1 gene. This alteration results from a A to G substitution at nucleotide position 340, causing the lysine (K) at amino acid position 114 to be replaced by a glutamic acid (E). 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

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Uncertain

0.053

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;T

Eigen

Benign

0.095

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.033

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.5

.;L

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.0

D;D

REVEL

Uncertain

0.32

Sift

Benign

0.089

T;D

Sift4G

Benign

0.18

T;T

Polyphen

0.25

B;B

Vest4

0.51

MutPred

0.46

Loss of ubiquitination at K114 (P = 0.0134);Loss of ubiquitination at K114 (P = 0.0134);

MVP

0.69

MPC

1.1

ClinPred

0.96

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.78

gMVP

0.20

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over