3-38224636-G-A

Position:

• chr3-38224636-G-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.768G>A​(p.Met256Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OXSR1 NM_005109.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.64

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=0.18859619).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OXSR1	NM_005109.3	c.768G>A	p.Met256Ile	missense_variant	8/18	ENST00000311806.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OXSR1	ENST00000311806.8	c.768G>A	p.Met256Ile	missense_variant	8/18	1	NM_005109.3	P1
OXSR1	ENST00000426620.5	c.*563G>A		3_prime_UTR_variant, NMD_transcript_variant	9/11	1
OXSR1	ENST00000446845.5	c.768G>A	p.Met256Ile	missense_variant	8/15	5
OXSR1	ENST00000483695.1	n.336G>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

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.768G>A (p.M256I) alteration is located in exon 8 (coding exon 8) of the OXSR1 gene. This alteration results from a G to A substitution at nucleotide position 768, causing the methionine (M) at amino acid position 256 to be replaced by an isoleucine (I). 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	0.27
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	.;T
Eigen	Benign	-0.042
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.035	.;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.24
Sift	Benign	0.056	T;D
Sift4G	Benign	0.20	T;T
Polyphen		0.0060	B;B
Vest4		0.42
MutPred		0.37		Loss of ubiquitination at K254 (P = 0.0573);Loss of ubiquitination at K254 (P = 0.0573);
MVP		0.61
MPC		0.84
ClinPred		0.94	D
GERP RS		5.4
Varity_R		0.63
gMVP		0.67

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: chr3-38266127;