20-44197369-C-G

Position:

• chr20-44197369-C-G

Variant summary

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

The NM_016470.8(OSER1):​c.562G>C​(p.Val188Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OSER1 NM_016470.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.952

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=0.09348947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSER1	NM_016470.8	c.562G>C	p.Val188Leu	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.562G>C	p.Val188Leu	missense_variant	4/4	1	NM_016470.8	ENSP00000255174.2
OSER1	ENST00000372970.6	c.562G>C	p.Val188Leu	missense_variant	6/6	3		ENSP00000362061.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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

Dec 03, 2021

The c.562G>C (p.V188L) alteration is located in exon 4 (coding exon 3) of the OSER1 gene. This alteration results from a G to C substitution at nucleotide position 562, causing the valine (V) at amino acid position 188 to be replaced by a leucine (L). 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	0.24
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.016	T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.014
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.093	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.060	N;N
REVEL	Benign	0.048
Sift	Benign	0.45	T;T
Sift4G	Benign	0.66	T;T
Polyphen		0.59	P;P
Vest4		0.064
MutPred		0.31		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.32
MPC		0.27
ClinPred		0.20	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.055
gMVP		0.15

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: chr20-42826009;