rs1822728207

Variant names:

• chr8-132024632-C-G
• rs1822728207
• NM_001080399.3:c.1283G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080399.3(OC90):​c.1283G>C​(p.Ser428Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S428G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OC90 NM_001080399.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0950
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10481274).

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.1283G>C	p.Ser428Thr	missense	Exon 14 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.1283G>C	p.Ser428Thr	missense	Exon 14 of 14	ENSP00000254627.3	Q02509-1
	ENSG00000258417	ENST00000262283.5	TSL:5	c.1919G>C	p.Ser640Thr	missense	Exon 18 of 18	ENSP00000262283.5	I6L893

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461274 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726902

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111712

Other (OTH) AF: 0.00 AC: 0 AN: 60324

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.2
DANN	Uncertain	0.98
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.095
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.088
Sift	Benign	0.094	T
Sift4G	Benign	0.24	T
Vest4		0.058
MVP		0.37
MPC		0.0032
ClinPred		0.17	T
GERP RS		2.8
Varity_R		0.065
gMVP		0.42
Mutation Taster		=89/11	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: rs1822728207; hg19: chr8-133036879;