rs776330059

Variant names:

• chr8-132024666-C-G
• rs776330059
• NM_001080399.3:c.1249G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-132024666-C-G
• chr8-132024666-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080399.3(OC90):​c.1249G>C​(p.Gly417Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,998 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OC90 NM_001080399.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.505

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05670297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OC90	NM_001080399.3	c.1249G>C	p.Gly417Arg	missense_variant	Exon 14 of 14	ENST00000254627.4	NP_001073868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OC90	ENST00000254627.4	c.1249G>C	p.Gly417Arg	missense_variant	Exon 14 of 14	2	NM_001080399.3	ENSP00000254627.3
ENSG00000258417	ENST00000262283.5	c.1885G>C	p.Gly629Arg	missense_variant	Exon 18 of 18	5		ENSP00000262283.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460998 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726758

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.6
DANN	Benign	0.46
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.22	T
PROVEAN	Benign	1.2	N;N
REVEL	Benign	0.065
Sift	Benign	0.44	T;T
Sift4G	Benign	0.48	T;T
Vest4		0.070
MVP		0.095
MPC		0.0031
ClinPred		0.087	T
GERP RS		1.3
Varity_R		0.027
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs776330059; hg19: chr8-133036913;