8-132041062-T-C

Variant names:

• chr8-132041062-T-C
• rs7386782
• NM_001080399.3:c.439A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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
• Publications: 25 publications found

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]

ENSG00000258417 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080399.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OC90	NM_001080399.3	MANE Select	c.439A>G	p.Ser147Gly	missense	Exon 6 of 14	NP_001073868.2	Q02509-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OC90	ENST00000254627.4	TSL:2 MANE Select	c.439A>G	p.Ser147Gly	missense	Exon 6 of 14	ENSP00000254627.3	Q02509-1
	ENSG00000258417	ENST00000262283.5	TSL:5	c.1027A>G	p.Ser343Gly	missense	Exon 9 of 18	ENSP00000262283.5	I6L893

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

GnomAD2 exomes AF: 0.731 AC: 181784 AN: 248724 AF XY: 0.728

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 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

African (AFR) AF: 0.743 AC: 24651 AN: 33166

American (AMR) AF: 0.772 AC: 34499 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 17860 AN: 26042

East Asian (EAS) AF: 0.762 AC: 30215 AN: 39638

South Asian (SAS) AF: 0.727 AC: 62523 AN: 85962

European-Finnish (FIN) AF: 0.734 AC: 39141 AN: 53356

Middle Eastern (MID) AF: 0.682 AC: 3907 AN: 5730

European-Non Finnish (NFE) AF: 0.713 AC: 782664 AN: 1097040

Other (OTH) AF: 0.715 AC: 42752 AN: 59806

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

African (AFR) AF: 0.743 AC: 30690 AN: 41318

American (AMR) AF: 0.751 AC: 11458 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2318 AN: 3464

East Asian (EAS) AF: 0.761 AC: 3876 AN: 5090

South Asian (SAS) AF: 0.723 AC: 3479 AN: 4814

European-Finnish (FIN) AF: 0.725 AC: 7620 AN: 10508

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.718 AC: 48724 AN: 67830

Other (OTH) AF: 0.710 AC: 1496 AN: 2108

Alfa AF: 0.717 Hom.: 179554

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 v4.9

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
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.48	N
PhyloP100		-0.17
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.027
Sift	Benign	0.54	T
Sift4G	Benign	0.10	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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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