20-44197473-G-A

Position:

• chr20-44197473-G-A

Variant summary

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

The NM_016470.8(OSER1):​c.458C>T​(p.Ser153Phe) 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: 33)
• Consequence: OSER1 NM_016470.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.50

Genes affected

OSER1 (HGNC:16105): (oxidative stress responsive serine rich 1) Predicted to be involved in cellular response to hydrogen peroxide. [provided by Alliance of Genome Resources, Apr 2022]

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=0.17647612).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSER1	NM_016470.8	c.458C>T	p.Ser153Phe	missense_variant	4/4	ENST00000255174.3	NP_057554.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSER1	ENST00000255174.3	c.458C>T	p.Ser153Phe	missense_variant	4/4	1	NM_016470.8	ENSP00000255174	P1
OSER1	ENST00000372970.6	c.458C>T	p.Ser153Phe	missense_variant	6/6	3		ENSP00000362061	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Aug 23, 2021

The c.458C>T (p.S153F) alteration is located in exon 4 (coding exon 3) of the OSER1 gene. This alteration results from a C to T substitution at nucleotide position 458, causing the serine (S) at amino acid position 153 to be replaced by a phenylalanine (F). 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	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.64	.;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	0.87	D;D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.079
Sift	Benign	0.11	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.19	B;B
Vest4		0.20
MutPred		0.50		Loss of phosphorylation at S153 (P = 0.005);Loss of phosphorylation at S153 (P = 0.005);
MVP		0.29
MPC		0.32
ClinPred		0.37	T
GERP RS		1.6
Varity_R		0.038
gMVP		0.33

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: chr20-42826113;