chr8-132041071-T-A

Variant names:

• chr8-132041071-T-A
• rs7386783
• NM_001080399.3:c.430A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080399.3(OC90):​c.430A>T​(p.Asn144Tyr) 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. 14/22 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: 0.0000096 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OC90 NM_001080399.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 21 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27182186).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OC90	NM_001080399.3	MANE Select	c.430A>T	p.Asn144Tyr	missense	Exon 6 of 14	NP_001073868.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OC90	ENST00000254627.4	TSL:2 MANE Select	c.430A>T	p.Asn144Tyr	missense	Exon 6 of 14	ENSP00000254627.3
	ENSG00000258417	ENST00000262283.5	TSL:5	c.1018A>T	p.Asn340Tyr	missense	Exon 9 of 18	ENSP00000262283.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000960 AC: 14 AN: 1457750 Hom.: 0 Cov.: 34 AF XY: 0.0000124 AC XY: 9 AN XY: 725496

African (AFR) AF: 0.00 AC: 0 AN: 33400

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1108298

Other (OTH) AF: 0.00 AC: 0 AN: 60226

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.25
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.038
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.039	D
Polyphen		0.67	P
Vest4		0.32
MutPred		0.43		Loss of disorder (P = 0.0295)
MVP		0.18
MPC		0.0064
ClinPred		0.70	D
GERP RS		1.1
Varity_R		0.096
gMVP		0.52
Mutation Taster		=91/9	polymorphism

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: rs7386783; hg19: chr8-133053318;