3-38224637-C-A

Position:

• chr3-38224637-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005109.3(OXSR1):​c.769C>A​(p.Leu257Met) 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. 14/21 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: OXSR1 NM_005109.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38

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]

ACMG classification

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=0.10016382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXSR1	NM_005109.3	c.769C>A	p.Leu257Met	missense_variant	8/18	ENST00000311806.8	NP_005100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OXSR1	ENST00000311806.8	c.769C>A	p.Leu257Met	missense_variant	8/18	1	NM_005109.3	ENSP00000311713.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1441830 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 717322

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.769C>A (p.L257M) alteration is located in exon 8 (coding exon 8) of the OXSR1 gene. This alteration results from a C to A substitution at nucleotide position 769, causing the leucine (L) at amino acid position 257 to be replaced by a methionine (M). 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	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.081	.;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.14	N;N
REVEL	Benign	0.031
Sift	Benign	0.23	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.18	B;B
Vest4		0.28
MutPred		0.34		Loss of methylation at K258 (P = 0.0321);Loss of methylation at K258 (P = 0.0321);
MVP		0.25
MPC		0.76
ClinPred		0.30	T
GERP RS		1.4
Varity_R		0.22
gMVP		0.64

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.

Other links and lift over

hg19: chr3-38266128;