chr8-132041062-T-C

Position:

• chr8-132041062-T-C

Variant summary

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

The NM_001080399.3(OC90):​c.439A>G​(p.Ser147Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 1,597,024 control chromosomes in the GnomAD database, including 414,573 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.

• Frequency:
  • Genomes: 𝑓 0.73 (40573 hom., cov: 32)
  • Exomes 𝑓: 0.72 (374000 hom.)
• Consequence: OC90 NM_001080399.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

Genes affected

OC90 (HGNC:8100): (otoconin 90) Predicted to enable calcium ion binding activity and structural molecule activity. Predicted to be involved in otolith mineralization. Predicted to be located in extracellular region. Predicted to be active in extracellular matrix. [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=1.3203876E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OC90	NM_001080399.3	c.439A>G	p.Ser147Gly	missense_variant	6/14	ENST00000254627.4	NP_001073868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OC90	ENST00000254627.4	c.439A>G	p.Ser147Gly	missense_variant	6/14	2	NM_001080399.3	ENSP00000254627	P1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110516 AN: 151468 Hom.: 40532 Cov.: 32

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.713

GnomAD3 exomes AF: 0.731 AC: 181784 AN: 248724 Hom.: 66654 AF XY: 0.728 AC XY: 98159 AN XY: 134914

Gnomad AFR exome AF: 0.744

Gnomad AMR exome AF: 0.774

Gnomad ASJ exome AF: 0.688

Gnomad EAS exome AF: 0.764

Gnomad SAS exome AF: 0.728

Gnomad FIN exome AF: 0.729

Gnomad NFE exome AF: 0.716

Gnomad OTH exome AF: 0.727

GnomAD4 exome AF: 0.718 AC: 1038212 AN: 1445440 Hom.: 374000 Cov.: 32 AF XY: 0.718 AC XY: 516759 AN XY: 720058

Gnomad4 AFR exome AF: 0.743

Gnomad4 AMR exome AF: 0.772

Gnomad4 ASJ exome AF: 0.686

Gnomad4 EAS exome AF: 0.762

Gnomad4 SAS exome AF: 0.727

Gnomad4 FIN exome AF: 0.734

Gnomad4 NFE exome AF: 0.713

Gnomad4 OTH exome AF: 0.715

GnomAD4 genome AF: 0.730 AC: 110614 AN: 151584 Hom.: 40573 Cov.: 32 AF XY: 0.729 AC XY: 53997 AN XY: 74046

Gnomad4 AFR AF: 0.743

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.710

Alfa AF: 0.711 Hom.: 94708

Bravo AF: 0.734

TwinsUK AF: 0.709 AC: 2629

ALSPAC AF: 0.714 AC: 2753

ESP6500AA AF: 0.750 AC: 3050

ESP6500EA AF: 0.717 AC: 6003

ExAC AF: 0.729 AC: 88078

Asia WGS AF: 0.733 AC: 2550 AN: 3478

EpiCase AF: 0.704

EpiControl AF: 0.704

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.74
DANN	Benign	0.49
DEOGEN2	Benign	0.039	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.25	T;T
MetaRNN	Benign	0.0000013	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.48	N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.92	N;N
REVEL	Benign	0.027
Sift	Benign	0.54	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.0	B;.
Vest4		0.12
MPC		0.0031
ClinPred		0.0036	T
GERP RS		0.41
Varity_R		0.039
gMVP		0.40

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: rs7386782; hg19: chr8-133053309; COSMIC: COSV51839846;