rs7386782

Positions:

• chr8-132041062-T-A
• chr8-132041062-T-C
• chr8-132041062-T-G

Variant summary

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

The NM_001080399.3(OC90):​c.439A>T​(p.Ser147Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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 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=0.22997954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OC90	NM_001080399.3	c.439A>T	p.Ser147Cys	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>T	p.Ser147Cys	missense_variant	6/14	2	NM_001080399.3	ENSP00000254627	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1453028 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723530

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: 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	Uncertain	0.45
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.37	T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Pathogenic	3.2	M;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.049
Sift	Benign	0.032	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.94	P;.
Vest4		0.38
MutPred		0.36		Loss of disorder (P = 0.0655);.;
MVP		0.29
MPC		0.0089
ClinPred		0.60	D
GERP RS		0.41
Varity_R		0.072
gMVP		0.55

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;