19-17226712-C-A

Variant names:

• chr19-17226712-C-A
• rs761673169
• NM_024578.3:c.89C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_024578.3(OCEL1):​c.89C>A​(p.Pro30Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000995 in 1,508,202 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P30L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: OCEL1 NM_024578.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

Genes affected

OCEL1 (HGNC:26221): (occludin/ELL domain containing 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

OCEL1 Gene-Disease associations (from GenCC):

• Aicardi syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Illumina

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.225553).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024578.3. 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
	OCEL1	NM_024578.3	MANE Select	c.89C>A	p.Pro30Gln	missense	Exon 2 of 6	NP_078854.1	Q9H607

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCEL1	ENST00000215061.9	TSL:1 MANE Select	c.89C>A	p.Pro30Gln	missense	Exon 2 of 6	ENSP00000215061.3	Q9H607
	OCEL1	ENST00000928402.1		c.89C>A	p.Pro30Gln	missense	Exon 2 of 6	ENSP00000598461.1
	OCEL1	ENST00000600232.5	TSL:5	c.83C>A	p.Pro28Gln	missense	Exon 2 of 6	ENSP00000469261.1	M0QXM2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152142 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 14 AN: 1356060 Hom.: 0 Cov.: 31 AF XY: 0.00000598 AC XY: 4 AN XY: 668358

African (AFR) AF: 0.00 AC: 0 AN: 28534

American (AMR) AF: 0.00 AC: 0 AN: 29182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20936

East Asian (EAS) AF: 0.0000278 AC: 1 AN: 35916

South Asian (SAS) AF: 0.00 AC: 0 AN: 73806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4122

European-Non Finnish (NFE) AF: 0.0000122 AC: 13 AN: 1069244

Other (OTH) AF: 0.00 AC: 0 AN: 55776

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152142 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74320

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.1
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.060
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.37
MutPred		0.23		Loss of catalytic residue at P30 (P = 0.003)
MVP		0.55
MPC		0.78
ClinPred		0.71	D
GERP RS		3.1
PromoterAI		-0.0053	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.14
gMVP		0.36
Mutation Taster		=96/4	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: rs761673169; hg19: chr19-17337521;