rs9346

Positions:

• chr20-44197710-A-C
• chr20-44197710-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016470.8(OSER1):​c.221T>G​(p.Val74Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,608,734 control chromosomes in the GnomAD database, including 34,241 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.26 (7546 hom., cov: 32)
  • Exomes 𝑓: 0.17 (26695 hom.)
• Consequence: OSER1 NM_016470.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.961

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.0824542E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSER1	NM_016470.8	c.221T>G	p.Val74Gly	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.221T>G	p.Val74Gly	missense_variant	4/4	1	NM_016470.8	ENSP00000255174.2
OSER1	ENST00000372970.6	c.221T>G	p.Val74Gly	missense_variant	6/6	3		ENSP00000362061.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40241 AN: 151980 Hom.: 7528 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.219

GnomAD3 exomes AF: 0.215 AC: 53983 AN: 251188 Hom.: 7779 AF XY: 0.216 AC XY: 29307 AN XY: 135794

Gnomad AFR exome AF: 0.526

Gnomad AMR exome AF: 0.128

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.430

Gnomad SAS exome AF: 0.334

Gnomad FIN exome AF: 0.185

Gnomad NFE exome AF: 0.141

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.168 AC: 244680 AN: 1456634 Hom.: 26695 Cov.: 32 AF XY: 0.172 AC XY: 124933 AN XY: 724884

Gnomad4 AFR exome AF: 0.528

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.193

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.265 AC: 40299 AN: 152100 Hom.: 7546 Cov.: 32 AF XY: 0.267 AC XY: 19879 AN XY: 74358

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.219

Alfa AF: 0.167 Hom.: 5854

Bravo AF: 0.273

TwinsUK AF: 0.136 AC: 505

ALSPAC AF: 0.142 AC: 549

ESP6500AA AF: 0.507 AC: 2235

ESP6500EA AF: 0.141 AC: 1215

ExAC AF: 0.224 AC: 27148

Asia WGS AF: 0.352 AC: 1225 AN: 3478

EpiCase AF: 0.145

EpiControl AF: 0.146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.61	.;T
MetaRNN	Benign	0.00031	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.036
Sift	Uncertain	0.018	D;D
Sift4G	Benign	0.17	T;T
Polyphen		0.062	B;B
Vest4		0.14
MPC		0.44
ClinPred		0.0074	T
GERP RS		1.0
Varity_R		0.11
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs9346; hg19: chr20-42826350; COSMIC: COSV54853461;